Late-life depression: evidence-based treatment and promising new directions for research and clinical practice.
As the population ages, successive cohorts of older adults will experience depressive disorders. Late-life depression (LLD) carries additional risk for suicide, medical comorbidity, disability, and family caregiving burden. Although response and remission rates to pharmacotherapy and electroconvulsive therapy are comparable with those in midlife depression, relapse rates are higher, underscoring the challenge to achieve and maintain wellness. This article reviews the evidence base for LLD treatment options and provides an analysis of treatment options for difficult-to-treat LLD variants (eg, psychotic depression, vascular depression). Treatment algorithms are also reviewed based on predictors of response and promising novel treatment options.


Minimal clinically important difference in patients who underwent decompression alone for lumbar degenerative disease.
The minimal clinically important difference (MCID) represents the smallest change in an outcome measure recognized as clinically meaningful to a patient after receiving a clinical intervention. Most studies that discussed the MCIDs for lumbar spinal stenosis (LSS) included mixed pathologies or procedures despite that the MCID value should be different depending on the intervention. Moreover, despite the efficacy of adopting percentage-change improvement for the MCID threshold, there are limited reports and discussions in the field of lumbar surgery. The aim of the present study was to elucidate the MCIDs for the Oswestry Disability Index (ODI), EuroQOL 5-dimension 3-level (EQ-5D-3L), physical component summary (PCS) of the Short Form of the Medical Outcomes Study, and Numeric Rating Scale (NRS) in patients with degenerative LSS treated with decompression surgery without fusion. A multicenter retrospective cohort study was performed. A total of 422 patients who underwent decompression surgery for LSS and answered a complete set of questionnaires were included in the study. Patients who underwent endoscopic or revision surgery were excluded. Preoperative and 1-year postoperative scores of each health-related quality of life questionnaires (HRQOLs) and patient satisfaction questionnaire response METHODS: The patient satisfaction question was used as an anchor, and the cutoff values were estimated based on absolute point improvement from baseline using a receiver-operating characteristic (ROC) curve analysis and the "mean change" method for MCIDs. The MCID values for percentage-change in HRQOLs were also calculated using ROC curve analysis. The three cutoff values for each HRQOL were validated using the Youden index for determining the most robust MCIDs. Of the patients, 356 (84.4%) were at least "somewhat satisfied" with the treatment results. The two cutoff values of absolute point-change in each HRQOL, which were estimated by two different anchor-based methods, were similar. The area under the curve of the ROC curve for percentage-change tended to be higher than that for absolute point-change. Moreover, the Youden index of the percentage-change in each HRQOL was higher than that of the absolute point-change calculated by either the "mean change" method or the ROC curve analysis. Based on these results, it was proposed that MCID was 42.4% for percentage-change in ODI, 22.0% for EQ-5D-3L, 13.7% for PCS, 25.0% for NRS (low back pain), 55.6% for NRS (leg pain), 22.2% for NRS (leg numbness). The MCIDs of HRQOLs were calculated in patients with LSS treated with decompression surgery without concomitant fusion procedure. The MCID cutoffs based on percentage-change from baseline were more effective than those of absolute point-change.


Correction: Lenalidomide added to standard intensive treatment for older patients with AML and high-risk MDS.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


[Clinical characteristics of patients with acute pulmonary embolism in high altitude area of Yunnan province in China].
Objective: To analyze the clinical features of patients with acute pulmonary embolism (APE) living in high altitude area of Yunnan province. Methods: This was a cross-sectional retrospective study. APE patients, hospitalized in our hospital between January 2017 and December 2019, were included. The selected patients were divided into low-risk group, medium-risk group and high-risk group according to risk stratification. The clinical data of patients, including demographic data, the main symptoms, risk factors of APE, heart rate and systolic blood pressure and laboratory testing results (D-dimer, cardiac troponin I (cTNI), N terminal B-type natriuretic peptide (NT-proBNP)) and echocardiography and electrocardiogram examination results, were obtained through the electronic medical record system. The clinical characteristics of selected patients were analyzed. Results: A total of 392 patients, aged (63.5±15.7) years, 224 males (57.14%), were included in this study and there were 59 low-risk, 304 medium-risk and 29 high-risk patients in this cohort. The main clinical manifestations were chest pain (157(40.05%)), dyspnea (107(27.30%)), hemoptysis (55(14.03%)), syncope as the first symptom (20(5.10%)), and only 6 cases (1.53%) presented with the typical "Virchow's triad". Most of the patients were accompanied by atypical chest tightness (223(56.89%)) and cough (208(53.06%)). The main risk factors were venous thrombosis of lower limbs (179(45.66%)), hypertension (138(35.20%)), surgery (63(16.07%)), and chronic obstructive pulmonary disease (COPD) (62(15.82%)). There were 57 cases (14.54%) of coronary heart disease, 57 cases (14.54%) of diabetes, 51 cases (13.01%) of cerebral infarction, 47 cases (12.00%) of advanced age, 15 cases (3.83%) of tumor, 7 cases (1.79%) of activity restriction, 6 cases (1.53%) of pregnancy and 4 cases (1.02%) of hormone use in this cohort. The proportion of lower extremity venous thrombosis was significantly higher in low-risk group than in medium-risk group (P<0.01), COPD was more common in high-risk and medium-risk groups than in low-risk group (P<0.01), hypertension was more common in high-risk group than in medium-and low-risk groups (P<0.01). The proportion of advanced age was significantly higher in medium-risk group than in low-risk group (P<0.01). There were no significant differences in RBC and hemoglobin level between low-, medium-and high-risk groups (P>0.05). The level of D-dimer was significantly higher in high-risk group than in medium-and low-risk groups (P<0.05). Levels of NT-proBNP and cTNI were significantly higher in high-risk group than in medium- and low-risk groups (P<0.05). Increased proportion of cTNI and NT-proBNP was significantly higher in high-risk group than in medium- and low-risk groups (P<0.05). There were 105 (26.79%) patients with pulmonary hypertension (PAH). The incidence of PAH was significantly higher in high-risk group than in low-risk group (P<0.01). There were 104 patients (26.53%) with right ventricular enlargement, and the incidence of right ventricular enlargement was significantly higher in high-risk group than in medium-and low-risk groups (P<0.01). Characteristic changes of electrocardiogram in patient with APE were T-wave inversion of limb leads (98(25.00%)), followed by SⅠQⅢTⅢ (83(21.17%)). Conclusions: The main clinical manifestations of APE in Yunnan high altitude area are chest pain and dyspnea, and syncope is the first symptom in some patients, but the typical "Virchow's triad" is rare. The most common risk factors are lower extremity venous thrombosis, hypertension, and COPD. Clinical symptoms, risk factors and laboratory examination results differ among patients with different risk stratification.


Synthesis and biological testing of 3,5-bis(arylidene)-4-piperidone conjugates with 2,5-dihydro-5H-1,2-oxaphospholenes.
Using the methodology of "click" chemistry, a series of conjugates of 3,5-bis(benzylidene)-1-(prop-2-yn)piperidin-4-ones with 4-alkyl-3-azidomethyl-2-ethoxy-2,5-dihydro-5H-1,2 oxaphosphol 2-oxides was synthesized. All newly obtained compounds 8-18 were characterized by 1H, 13C, 31P, 19F NMR and IR spectroscopy. The potential antitumor activity of the synthesized conjugates8-18was studied in terms of their ability to influence the viability of variouscancercell lines, including A549, SH-SY5Y, Hep-2, and HeLa. Compound 15, which contains two fluorine atoms in the benzene ring, was shown to be the most promising. The mechanism of the cytotoxic action of this conjugate is supposed to be associated with the ability to inhibit the glycolytic profile of transformed cells.


Spoilage potential of bacterial species from chilled vacuum-packed lamb.
The objective of this study was to establish whether specific organisms play important roles in the spoilage rate of vacuum-packed (VP) lamb at low storage temperatures. The spoilage potential of representative organisms (n = 13) of the spoilage community of VP lamb were investigated through a series of shelf-life challenge trials. Each isolate was individually inoculated onto sterile (irradiated) and non-sterile (i.e., containing natural microbial community) VP lamb meat. Meat quality was assessed over time by measuring sensorial qualities, bacterial growth and pH. Among all test organisms, Clostridium spp. had the highest spoilage potential and had a major effect on the spoilage rate of VP lamb (based on sensory assessment). C. estertheticum caused premature 'blown pack' spoilage; however, the spoilage was delayed in a community setting. C. putrefaciens and C. algidicarnis caused premature spoilage of VP lamb independently and in a community setting. In contrast, all facultative anaerobes and Pseudomonas sp. tested were not capable of spoiling meat independently or within a community, expect for Carnobacterium divergens and Serratia spp., which spoiled meat prematurely when present in a community. Overall, these results highlight that Clostridium could be one of the main taxa driving the faster rate of quality loss of chilled VP lamb compared to beef. This research can help to inform opportunities for shelf-life extension by targeting organisms with 'high' spoilage potential, such as Clostridium.


The Predictive Value of Social Frailty on Adverse Outcomes in Older Adults Living in the Community.
Older people are often socially deprived, which may predispose them to frailty. The aim of the study was to identify the independent effects of social deficits and their combined effects with frailty ("social frailty") in predicting functional decline, institutionalization, and mortality in older adults living in the community. Longitudinal study with a 3-year follow-up. A nationally representative sample of community-dwelling older people aged 65 years or older in South Korea (N = 11,241). Social deficits were defined as deficiencies in socioeconomic status, living situation, social network size, contact with social networks, social support, and social activities. The number of social deficits was categorized as none (0), low (1-2), and high (3 or more), based on the summated score. Frailty status was defined using the Fried criteria. Cox proportional hazards model was used to analyze the effects of the increasing levels of social deficits on functional decline, institutionalization, and mortality. The combined effects of both social deficits and physical frailty were also assessed, controlling for covariates. The prevalence of frailty was 7.7%, with 49.1% being prefrail at baseline. Overall, the presence of social deficits tended to elevate the risk of adverse outcomes, where acquiring 1 social deficit was associated with an 11% to 27% increase in their risks. In the multivariable analysis, those with a high level of social deficits demonstrated a significantly elevated mortality risk [hazard ratio (HR) = 1.45, 95% confidence interval (CI): 1.07, 1.97). There was a trend toward increasing hazards when social deficits were combined with physical frailty, with the group having a high level of social deficits and being frail exhibiting the highest mortality risk (HR = 3.14, 95% CI: 1.81, 5.46). Social adversity independently predicted mortality. When combined with physical frailty, an accumulation of social deficits increased the predictive value.


Effects of dopamine and selective dopamine agonists upon platelet accumulation in the cerebral and pulmonary vasculature of the rabbit.
1. A selection of novel compounds were shown to exhibit dopaminergic activity in vitro. 2. 111Indium-labelled platelets were continuously monitored in the cerebral and pulmonary vasculature of anaesthetized rabbits. The effects of dopamine and selective dopamine receptor agonists on ADP and thrombin induced platelet accumulation were recorded. 3. Pretreatment with dopamine (2 mg kg(-1) min(-1), i.v.) significantly reduced ADP (20 microg kg(-1), i.v.) induced platelet accumulation in the pulmonary vasculature whereas lower doses had no effect. 4. Dopamine (100 microg kg(-1) min(-1) intra-carotid, i.c.) potentiated thrombin (90 u kg(-1), i.c.) induced platelet accumulation in the cerebral vasculature whereas higher doses (1-2 mg kg(-1) min[-1]) inhibited accumulation. 5. The selective dopamine receptor agonists tested did not significantly inhibit platelet accumulation induced by ADP or thrombin. Two of these selective agonists, at doses higher than the intended therapeutic doses, induced thrombocytopaenia and an associated increase in platelet accumulation in the lung in response to thrombin. 6. These results extend previous in vitro studies regarding the dual actions of dopamine upon platelets and show for the first time the effects of selective dopamine receptor agonists upon platelet aggregation in vivo.


Non-coding Regions of Mitochondrial DNA and the cox1 Gene Reveal Genetic Variability Among Local Belarusian Populations of the Causative Agent of Cercarial Dermatitis, Bird Schistosome Trichobilharzia szidati (Digenea: Schistosomatidae).
The cercariae of avian blood flukes Trichobilharzia szidati (Digenea, Schistosomatidae) are known to cause cercarial allergic dermatitis ("swimmer's itch") in humans. Global epidemics can have significant impacts on local tourism-related economies in recreational areas. Little is known about the genetic polymorphism of the parasite population, or about the variability of the non-coding regions of mitochondrial DNA (mtDNA) and the possibility of using this as a genetic marker. The T. szidati cercariae were collected over 7 years from 33 naturally infected Lymnaea stagnalis snails from five sites at two neighboring lakes in Belarus. We investigated the variability of the short (SNR) and long (LNR) non-coding regions of mt DNA and the genetic diversity within the 1125-bp sequences of the gene for subunit 1 of cytochrome c oxidase (cox1). In the SNR sequences, we found only length variability caused by changes in the number of bases in the mononucleotide tracts T6-T8. LNR demonstrates high variability in nucleotide sequence length (182-260 bp) depending on the presence of two long deletions of 59 and 78 nucleotides. Both mitochondrial loci (LNR and cox1) are characterized by high haplotype diversity (H = 0.922 and H = 1.0, respectively); the nucleotide diversity is significantly higher for LNR (π = 1.926 ± 0.443) compared to cox1 (π = 0.704 ± 0.059). Phylogenetic reconstructions based on the variability of each of the loci (LNR and cox1) and their concatenated sequences revealed their shallow structure and the absence of a correlation between the distribution of single-nucleotide polymorphisms and the geographic origin of parasites from two Belarusian lakes. We identified at last four weakly sublineages in the phylogenetic pattern of T. szidati. The carriers of each deletion have specific patterns for each of the two loci and form their own phylogeographic sublineages. An association between two fixed LNR substitutions and a fixed non-synonymous substitution in cox1 was found in four representatives of one lineage that had a short deletion in the LNR. This study clarified the phylogeographic structure of the Belarusian population of T. szidati. Our data provide the basis for the use two mt markers in large-scale population studies of the parasite, as well as for studying the molecular evolution of coding and non-coding mtDNA in trematodes.


The growth rate and clinical outcomes of radiation induced meningioma undergoing treatment or active monitoring.
Radiation induced meningioma (RIM) incidence is increasing in line with improved childhood cancer survival. No optimal management strategy consensus exists. This study aimed to delineate meningioma growth rates from tumor discovery and correlate with clinical outcomes. Retrospective study of patients with a RIM, managed at a specialist tertiary neuroscience center (2007-2019). Tumor volume was measured from diagnosis and at subsequent interval scans. Meningioma growth rate was determined using a linear mixed-effects model. Clinical outcomes were correlated with growth rates accounting for imaging and clinical prognostic factors. Fifty-four patients (110 meningiomas) were included. Median duration of follow-up was 74 months (interquartile range [IQR], 41-102 months). Mean radiation dose was 41 Gy (standard deviation [SD] = 14.9) with a latency period of 34.4 years (SD = 13.7). Median absolute growth rate was 0.62 cm3/year and the median relative growth rate was 72%/year. Forty meningiomas (between 27 patients) underwent surgical intervention after a median follow-up duration of 4 months (IQR 2-35). Operated RIMs were clinically aggressive, likely to be WHO grade 2 at first resection (43.6%) and to progress after surgery (41%). Median time to progression was 28 months (IQR 13-60.5). A larger meningioma at discovery was associated with growth (HR 1.2 [95% CI 1.0-1.5], P = 0.039) but not progression after surgery (HR 2.2 [95% CI 0.7-6.6], P = 0.181). Twenty-seven (50%) patients had multiple meningiomas by the end of the study. RIMs exhibit high absolute and relative growth rates after discovery. Surgery is recommended for symptomatic or rapidly growing meningiomas only. Recurrence risk after surgery is high.


Bromocriptine treatment of the premenstrual syndrome.
Bromocriptine, 2.5 mg twice a day was tested for its effect on premenstrual tension in a random double-blind cross-over trial. 1. The compound tended to lessen the symptoms, especially mastodynia. 2. Serum prolactin levels around the upper limit of the normal range were significantly lowered. Patients with the highest starting prolaction levels had the most severe symptoms and in these patients the fall in the levels was greatest. 3. Serum FSH and LH levels were significantly reciprocally influenced compared with serum prolactin. Serum estradiol-17-beta and progesterone did not change during treatment. 4. The bromocriptine-treated cycles were all ovulatory according to basal temperature levels. The luteal phase was prolonged when serum FSH was raised.


Association of MTHFR 677C>T and 1298A>C polymorphisms with susceptibility to autism: A systematic review and meta-analysis.
Several studies have investigated association of MTHFR 677C > T and 1298A > C polymorphisms with risk of autism, but they have reported controversial and inconclusive results. The present meta-analysis was designed to evaluate association of MTHFR 677C > T and 1298A > C polymorphisms with risk of autism. A comprehensive literature search was done in PubMed, EMBASE, and CNKI databases to identify all eligible publications up to April 01, 2019. Finally, 25 case-control studies including 18 studies on MTHFR 677C > T and 7 studies on MTHFR 1298A > C polymorphism were selected. Overall, a significant association was found between MTHFR 677C > T and an increased risk of autism under all five genetic models (T vs. C: OR = 1.483, 95% CI 1.188-1.850, p ≤ 0.001; TT vs. CC: OR = 1.834, 95% CI 1.155-2.913, p = 0.010; TC vs. CC: OR = 1.512, 95% CI 1.101-2.078, p = 0.011; TT + TC vs. CC: OR = 1.632, 95% CI 1.261-2.113, p ≤ 0.001; and TT vs. TC + CC: OR = 1.427, 95% CI 1.002-2.032, p = 0.049). However, no significant association was found between MTHFR 1298A > C and autism risk. Stratified analyses showed that MTHFR 677C > T and 1298A > C polymorphisms are involved in genetic susceptibility of autism by ethnicity. Results of this meta-analysis indicated that MTHFR 677C > T polymorphism may be associated with increased risk of autism in overall and by ethnicity, while MTHFR 1298A > C was reported to be significantly associated with the risk of autism only in Caucasians. MTHFR polymorphisms could be used as a diagnostic marker for autism with respect to ethnicity background.


Comparative evaluation of a latex test for the identification of Staphylococcus aureus.
A rapid latex agglutination test, Staphaurex, was tested for its ability to identify Staphylococcus aureus using 72 reference strains and 785 clinical isolates of the family Micrococcaceae. All reference strains of Staphylococcus aureus were Staphaurex-positive. Non-Staphylococcus aureus reference strains were negative. Using clinical strains, the results of the Staphaurex test were compared with the results of other tests commonly used to identify Staphylococcus aureus. A total of 393 clinical isolates were classified as Staphylococcus aureus. The Staphaurex, slide coagulase, tube coagulase/human plasma and tube coagulase/rabbit plasma tests correctly identified 98%, 93.6%, 93.6% and 97.5% of the Staphylococcus aureus strains, respectively. The performance of the Staphaurex test, in terms of sensitivity and specificity, was significantly better than the slide coagulase test. It was as sensitive and almost as specific as the tube coagulase rabbit test and more sensitive than the tube coagulase human test.


Phytochemical profile and antioxidant capacity, α-amylase and α-glucosidase inhibitory activities of Oxalis pes-caprae extracts in alloxan-induced diabetic mice.
Diabetes and its complications are closely correlated with chronic hyperglycemia, causing severe oxidative stress and leading to glycation reaction with formation of advanced glycation end products. However, medicinal plants are still a source of inspiration for the discovery of new treatments of several diseases, including diabetes. The present study was aimed to evaluate the antioxidant and antidiabetic properties of Oxalis pes-caprae flowers extract in alloxan-induced diabetic mice. The phytochemical and antioxidant activities of both aqueous and methanolic extracts were assessed by in-vitro testing such as free radical scavenging assays (DPPH and ABTS+), ferrous ions (Fe2+) chelating activity and reducing power assay. Additionally, the detection of Amadori products and advanced glycation end products was used to determine the antiglycation potential. α-glucosidase and α-amylase inhibitory assessment was employed to determine the antidiabetic effect, while alloxan-induced diabetic mice were used to measure the in-vivo activities of antioxidants and carbohydrates enzymes. The effect of the methanolic extract on body weight and blood glucose level of extract-treated diabetic mice were also investigated. Among the tested extract, the methanolic extract was the richest in phenolic compounds which is directly related with their remarkable antioxidant, enzyme inhibitory and antiglycation activity. The oral administration of the two doses of Oxalis pes-caprae flowers (150 mg/kg and 250 mg/kg) daily for 3 weeks resulted in hypoglycemic effect compared to the reference drug, glibenclamide (10 mg/kg). Furthermore, the extract was shown to significantly increase the activities of antioxidants and glycolysis enzymes in the liver, kidney and spleen of diabetic mice, compared to diabetic control group. Therefore, Oxalis pes-caprae extract effectively exhibited hypoglycemic and antidiabetic effects as indicated by in-vitro and in-vivo studies, confirming the protective effects on hyperglycemia and oxidative damage.


Immunohistochemical staining of GLUT1 in benign, borderline, and malignant ovarian epithelia.
Aberrant expression of the facilitative glucose transporter GLUT1 is found in a wide spectrum of epithelial malignancies. The authors describe an immunohistochemical study of GLUT1 expression in benign, borderline, and malignant ovarian epithelia. One hundred forty one formalin-fixed, paraffin-embedded sections were immunostained with rabbit anti-GLUT1 using the streptavidin-biotin method. The samples were as follows: 3 endometriotic cysts, 9 serous cystadenomas, 15 mucinous cystadenomas, 17 noninvasive borderline implants, 3 invasive borderline implants, and 3 endosalpingiosis. In addition, 35 borderline tumors (26 serous, 7 mucinous, 2 seromucinous) and 56 adenocarcinomas (50 serous, 4 endometrioid, 2 mucinous) were stained. Benign serous and mucinous cystadenomas and endosalpingiosis were non-staining with GLUT1 antiserum. Twenty-eight of 35 borderline tumors (80%) stained positively, with weak to moderate (1-2+ out of 3) staining intensity and focal or patchy distribution. Seventeen noninvasive serous borderline implants were negatively stained; however, three invasive serous borderline implants were positively stained with GLUT1 antiserum. Fifty four of 56 ovarian carcinomas (96%) stained positively, with moderate to strong (2-3+ out of 3) intensity and multifocal distribution. GLUT1 is a consistent marker of ovarian epithelial malignancy. GLUT1 staining is absent in benign ovarian epithelial tumors, and shows progressively more staining in invasive tumors as compared to borderline tumors. Anti-GLUT1 antibody may be useful in distinguishing invasive from noninvasive serous borderline implants.


Idiopathic aortitis: an underrecognized vasculitis.
Aortitis is a general term denoting inflammation of the aortic wall. Various infectious and non-infectious diseases can be complicated by aortitis; in addition, isolated idiopathic aortitis has also been described. In a 12-year nationwide Danish population-based study, the prevalence of aortitis among 1,210 resected thoracic aorta samples was 6.1%, with nearly three-quarters of cases being idiopathic. Identified risk factors for aortitis included advanced age, a history of connective tissue disease, diabetes mellitus, and heart valve pathology. As in virtually all pathological studies, this study has a bias toward reporting the most severe cases of aortitis requiring surgical repair.


RssB-mediated σS Activation is Regulated by a Two-Tier Mechanism via Phosphorylation and Adaptor Protein - IraD.
Regulation of bacterial stress responding σS is a sophisticated process and mediated by multiple interacting partners. Controlled proteolysis of σS is regulated by RssB which maintains minimal level of σS during exponential growth but then elevates σS level while facing stresses. Bacteria developed different strategies to regulate activity of RssB, including phosphorylation of itself and production of anti-adaptors. However, the function of phosphorylation is controversial and the mechanism of anti-adaptors preventing RssB-σS interaction remains elusive. Here, we demonstrated the impact of phosphorylation on the activity of RssB and built the RssB-σS complex model. Importantly, we showed that the phosphorylation site - D58 is at the interface of RssB-σS complex. Hence, mutation or phosphorylation of D58 would weaken the interaction of RssB with σS. We found that the anti-adaptor protein IraD has higher affinity than σS to RssB and its binding interface on RssB overlaps with that for σS. And IraD-RssB complex is preferred over RssB-σS in solution, regardless of the phosphorylation state of RssB. Our study suggests that RssB possesses a two-tier mechanism for regulating σS. First, phosphorylation of RssB provides a moderate and reversible tempering of its activity, followed by a specific and robust inhibition via the anti-adaptor interaction.


Neglected Achilles Tendon Ruptures.
Achilles tendon ruptures are a common ailment and often missed in upwards of 25% of cases. Neglected Achilles injuries can be treated both conservatively and surgically. Physical therapy, bracing, and custom ankle-foot orthoses are some options to consider. Surgically, there are many options, depending on the quality of the existing tendon, size of the defect, and the surgeon's comfort with the technique. Those procedures include primary repair, V-Y tendon advancement, turndown flap, tendon transfers, and other allografts. These techniques have been shown to have good to excellent outcomes and typically return patients to activities without complaints.


Membrane associated events during proliferative inhibition of granulocyte precursors.
A new way of assessing the significance of intracellular signals that may regulate cellular proliferation, would be to analyze possible 'second messengers' when proliferation is slowed down, rather than stimulated. Therefore, we examined proliferating mononuclear blood cells from leukaemic patients which had been exposed to an inhibitory ox leucocyte extract. The extract decreased 3H-thymidine incorporation in leukaemic cells in short-term cultures. The inhibition was not cell-line specific, but was nevertheless non-toxic and not due to endotoxin. The K+ flux into the leukaemic cells was assessed with 86Rb+, a K+ analogue. An inverse relationship was found between 86Rb+ uptake and 3H-thymidine incorporation. The increased 86Rb+ influx was probably due to leakage or exchange mechanisms other than the Na+/K+ membrane pump, as suggested by ouabain inhibition experiments. However, the long lag time (greater than 45 min) between addition of inhibitor and a marked increase in 86Rb+ uptake does not support a role for the K+ flux as an early mediator of the inhibitory signal.


Surface atrial frequency analysis in patients with atrial fibrillation: assessing the effects of linear left atrial ablation.
Our group has shown previously that measurements of atrial frequency can be obtained from surface 12-lead ECG recordings of patients during atrial fibrillation (AF), using a combination of principal component and Fourier transform algorithms. Such measurements are reproducible over time and change with drug manipulation of the arrhythmia. To determine whether linear left atrial ablation, using a combination of "roof" and "mitral isthmus" lines results in changes in surface atrial frequency during AF and to assess the contribution of each individual line when sited sequentially. Computerized recordings from 26 patients, who had undergone linear ablation procedures for AF, were reviewed. The atrial signal was extracted from the 12-lead ECG data by principal component analysis and the main frequency component identified using Fourier analysis. Atrial frequency before and after these two standard ablation lines was compared. Atrial frequency decreased significantly after the combination of roof and mitral isthmus lines (5.66 vs 5.15 Hz) and when either roof (5.61 vs 5.13 Hz) or mitral isthmus (5.89 vs 5.75 Hz) lines were sited first. However, only the roof line led to a significant reduction in atrial frequency when sited second (5.64 vs 5.49 Hz). Measurements of atrial frequency can be obtained from surface 12-lead ECG recordings during AF and change as predicted in response to linear left atrial ablation. This technique may be useful in assessing antiarrhythmic treatments for AF.


Bone density in women: college athletes and older athletic women.
Bone density was studied in intercollegiate athletes and older athletic women. Single-photon densitometry was used to assess bone density parameters at a new distal radial site, the midradius, and the first metatarsus. Dual-photon densitometry assessed bone density of the lumbar spine. Eleven intercollegiate tennis players, 23 swimmers, and 86 older "athletic" women from 23 to 75 years of age were compared with age-matched nonathletic controls. "Athletic" describes adult women who exercised at least three times per week, 8 or more months of the year, for a minimum of 3 years. The radius and metatarsus bone content of intercollegiate athletes was significantly above control values. Lumbar spine density was significantly higher only in tennis players. Mean bone density values for adult "athletic" women were also significantly greater than in age-matched controls. In the oldest athletic group (55-75 years of age) bone measurement values in radius and lumbar spine were in the same range as for younger "athletic" women. In contrast, after 50 years of age, these values in the control population decreased by 0.7%/year. Therefore the largest variance (increase) from age-matched controls occurred in the oldest "athletic" group. Also, we have established a distal radial density value (using our modified site) below which we consider women "at risk" and recommend further bone health evaluation. Only two adult athletic women greater than 55 years of age fell into this category. It is concluded from this cross-sectional study that a regularly maintained athletic program for adult women may reduce the rate of "normal" bone mass loss accompanying age, particularly postmenopausally.(ABSTRACT TRUNCATED AT 250 WORDS)


Secretion of coagulant factor VIII activity and antigen by in vitro cultivated rat liver sinusoidal endothelial cells.
Different types of liver cells and a few extrahepatic cell types were analysed for the presence and production of factor VIII activity (VIII:C). Only freshly prepared suspensions of rat liver sinusoidal cells and pure monolayer cultures of rat liver endothelial cells (LEC) were found to contain and secrete detectable amounts of the coagulation factor. Secretion of VIII:C by cultured LEC was inhibited by cycloheximide and by monensin. Constant levels of VIII:C were produced for at least 48 h suggesting continuous synthesis rather than a burst release of stored material. VIII:C, as measured spectro-photometrically by conversion of X to Xa, was inhibited by anti-human VIII:C antiserum. Indirect immunocytochemistry using this antiserum gave positive staining only with LEC. Immunoprecipitation of metabolically labelled proteins in conditioned rat LEC medium with the anti human VIII:C antiserum revealed the presence of proteins of similar sizes to those reported for human VIII:C. These results indicate that rat LEC are an important site for production and secretion of procoagulant factor VIII and are not only a site for storage and release of the factor. The established conditions for synthesis of VIII:C in in vitro cultivated rat LEC should provide the means to study the regulation of VIII:C synthesis.


Abnormalities among offspring of oral and nonoral contraceptive users.
An analysis of 223 children born between 1961 and 1965 to 5,465 women in a controlled experiment at the University of Puerto Rico School of Medicine, regarding the use of oral and nonoral contraceptives, failed to reveal any statistical differences in birth weight and physical abnormalities between the two contraceptive groups. The mean birth weight for the oral group was 7 pounds, 4.1 ounces, whereas for the nonoral group it was 7 pounds, 5.4 ounces. Abnormal physical findings were 10.7% for the oral group and 16.7% for the nonoral group. A comparison is also made between the two groups with respect to incidence of abnormalities by socioeconomic class and by sex of the child, as well as by the number of pregnancies and age of the mother. No significant differences were noted between the groups as an indication of the effect of oral contraceptives.


Phase separation, charge separation and biogenesis.
The current view of bioenergetics postulates transmembrane charge separation as a primary mechanism of energy storage and transformation. Using that bioenergetic view we examine possible methods of photon driven transduction in primordial vesicles. Two possible types of proton pumps are analyzed and a method of anaerobic photophosphorylation is discussed. Using these principles we theorize about the formation of prebiotic photochemical vesicles utilizing the same transmembrane energy conversions characteristic of contemporary cellular systems.


Novel use of a short-acting intravenous beta blocker in combination with inotropic therapy as a bridge to chronic oral beta blockade in patients with advanced heart failure.
The role for beta blockers in advanced heart failure (New York Heart Association class IV) remains undefined because of concerns about tolerability and uncertainty about efficacy. We report the use of a short-acting intravenous beta blocker in combination with inotropic therapy as a means to bridge five patients with advanced heart failure to chronic oral beta blockade; two of these patients had been chronically managed with intravenous inotrope. At 4 months' follow-up, all patients remained on beta-blocker therapy and none was hospitalized for heart failure or had received intravenous diuretics. Given the early separation of survival curves in the randomized clinical trials of beta blockers in heart failure, it is possible that these patients will accrue a survival benefit. We conclude that some patients with advanced heart failure can be offered oral beta-blocker therapy by bridging with a combination of intravenous inotrope and short-acting intravenous beta blocker.


Ichthyosis: case report in a Colombian man with genetic alterations in ABCA12 and HRNR genes.
Ichthyosis is a heterogeneous group of diseases caused by genetic disorders related to skin formation. They are characterized by generalized dry skin, scaling, hyperkeratosis and frequently associated with erythroderma. Among its different types, harlequin ichthyosis (HI) stands out due to its severity. HI is caused by mutations in the ABCA12 gene, which encodes essential proteins in epidermal lipid transport, and it helps maintain the homeostasis of the stratum corneum of the epidermis. However, due to the wide spectrum of genetic alterations that can cause ichthyosis, holistic medical care, and genetic studies are required to improve the diagnosis and outcomes of these diseases. Here, we presented the case of a 19 years old male patient who was a premature infant and exhibited clinical features consistent with HI, including bright yellow hyperkeratotic plates with erythematous fissures that covered his entire body like a collodion baby. Currently, he exhibited erythroderma, photosensitivity, ectropion, auricular pavilion alterations, and musculoskeletal disorders, such as equinovarus feet, fingers, hands, and hypoplastic feet with contractures in flexion and marked difficulty in fine motor skills. In addition, he presented dyschromatopsia, Achilles reflex hyporeflexia, slight speech, dental alteration and deficient cognitive performance. After the genetic sequencing, variants were found in ABCA12 and HRNR which are related to several skin diseases, including ichthyosis. Although in clinical practice, ichthyosis is a common entity, a severe type of ichthyosis is presented, highlighting the importance of appropriate genetic diagnosis, given the broad spectrum of genetic alterations with similar phenotypic and clinical characteristics. These pathologies must be known to guarantee initial support measures to prevent complications and offer multidisciplinary management to those patients.


Qualitative Study on Diversity, Equity, and Inclusion Within Radiation Oncology in Europe.
Organizational culture plays a major role in prioritizing diversity, equity, and inclusion (DEI) objectives by aligning individual values of employees with organizational values. However, effective strategies to create an inclusive organizational culture, in which these values are aligned, remain unclear. The European Society for Radiotherapy and Oncology (ESTRO) launched a qualitative study, as a follow-up of the previous project on DEI that highlighted low levels of inclusion and work engagement among radiation oncology (RO) professionals in Europe. The aim of the present study was to gain an understanding of how DEI could be improved within RO departments by creating a more inclusive organizational culture. A qualitative research study was conducted by enrolling RO professionals from 4 selected European countries through an open call on the ESTRO platform. Respondents who completed an online survey and met the inclusion criteria, such as experiencing low DEI levels at work, were invited for an online semistructured interview. Interview transcripts were analyzed thematically with an abductive approach via concepts in relation to "DEI," "work engagement," "organizational culture," and "professional values." Twenty-six eligible respondents from Great Britain, Italy, Poland, and Switzerland were interviewed. The thematic analysis identified cases in which limited engagement at work emerged when the personal values of RO professionals conflicted with dominant organizational values, hampering DEI. Three conflicts were found between the following personal versus organizational values: (1) self-development versus efficiency, (2) togetherness versus competition, and (3) people-oriented versus task-oriented cultures. Awareness of how organizational values can conflict with professionals' values should be raised to improve inclusion and engagement in the workplace. Additionally, efforts should be focused on tackling existing power imbalances that hamper effective deliberation on organizational- versus personal-value conflicts.


Value-based eating habits; exploring religio-cultural nutritional behavior norms.
Defining a standard norm is critical in nutritional cognitive-behavioral interventions. These norms can be derived from a statistical or value-based point of view. Religion and subsequent cultural values can have significant effects on social behaviors, especially on eating habits. In this study, the authors quantify the presence of religio-cultural nutritional behavior norms in Abrahamic scriptures. Qualitative content analysis and descriptive analysis were applied to these texts to provide a better understanding of the subject. The extracted norms were categorized into nine main behavioral domains, and most of the observed value-based norms were in agreement with previous experimental researches. There is strong emphasis on nutritional habits in value-based religio-cultural sources. The use of these norms in later policies and practices is advised. This approach can lead to healthier nutritional choices and a decrease in non-communicable diseases.


Venous Thromboembolism in Patients with Thermal Injury: A Review of Risk Assessment Tools and Current Knowledge on the Effectiveness and Risks of Mechanical and Chemical Prophylaxis.
Venous thromboembolism (VTE) can be a life-threatening or limb-threatening complication of thermal injury. The severity of burn injury can be used to predict VTE risk among patients with thermal injury, and a weighted risk-stratification tool has been developed. This article reviews the incidence, diagnosis, and management of thromboembolic events in patients with burns. The article particularly focuses on identifying those patients who are at highest risk for VTE and provides recommendations on mechanical and chemical prophylaxis.


Affordability of Canada's Food Guide: Current challenges amid COVID-19, War in Ukraine, and other world events.
Since the 2019 Canada Food Guide was released, there have been concerns raised over the cost of food, with an emphasis on the affordability of nutritious food. In this study, we evaluate the affordability of the 2019 Canada Food Guide in relation to the previous edition from 2007. As a result of the pandemic and other significant world events, many are feeling financial stress as prices in many areas of life rise, including housing, gas, and food. Our results show that it is more cost-effective, on average, for children and teens to follow the 2019 Canada Food Guide, but more expensive for adults, when compared to the 2007 edition.


A novel interpolation method to predict soil heavy metals based on a genetic algorithm and neural network model.
To improve the prediction accuracy of soil heavy metals (HMs) by spatial interpolation, a novel interpolation method based on genetic algorithm and neural network model (GANN model), which integrates soil properties and environmental factors, was proposed to predict the soil HM content. Eleven soil HMs (Cu, Pb, Zn, Cd, Ni, Cr, Hg, As, Co, V and Mn) were predicted using the GANN model. The results showed that the model had a good prediction performance with correlation coefficients (R2) varying from 0.7901 to 0.9776. Compared with other traditional interpolation methods, including inverse distance weighting (IDW), ordinary kriging (OK), universal kriging (UK), and spline with barriers interpolation (SBI) methods, the GANN model had a relatively lower root mean square error value, ranging from 0.0497 to 77.43, suggesting that the GANN model might be a more accurate spatial interpolation method and the soil properties together with the environmental geographical factors played key roles in prediction of soil HMs.


Efficacy of intralesional injections of platelet-rich plasma in patients with oral lichen planus: A pilot randomized clinical trial.
To evaluate the clinical efficacy of intralesional platelet-rich plasma (PRP) injections compared to intralesional triamcinolone acetonide (TA) injections in the treatment of erosive oral lichen planus (EOLP). Twenty patients with EOLP were assigned randomly to either PRP or TA group. Patients received weekly intralesional injections for 4 weeks, and then followed up for 3 months on regular visits every 2 weeks. Pain scores using numerical pain score and clinical score were recorded by a blinded assessor each visit for all patients and remission score at the end of the trial was recorded. Both groups showed significant improvement in the clinical parameters (pain and clinical score) "p = .001." Regarding remission of the lesions, 80% of patients in the PRP group showed complete remission compared to 70% in the TA group. However, there is no statistical significance when comparing the two groups in pain score, clinical score, or remission. PRP injections could be considered as an effective alternative single treatment modality for EOLP. The protocol for this study registered in Clinicaltrials.gov registry under the identifier number: NCT03293368.


Introduction to the use of baculoviruses as biological insecticides.
Baculoviruses are widely used both as protein expression vectors and as insect pest control agents. This section provides an overview of the baculovirus lifecycle and use of baculoviruses as insecticidal agents. This chapter includes discussion of the pros and cons for use of baculoviruses as insecticides, and progress made in genetic enhancement of baculoviruses for improved insecticidal efficacy. Formulation and application of baculoviruses for pest control purposes are described elsewhere.


Risk-benefit assessment of anticoagulant therapy.
Thromboembolic disease is a common medical condition which, if untreated, carries a significant risk of morbidity and mortality. Treatment with anticoagulant therapy, while clearly beneficial, may expose patients to potentially serious side effects. A thoughtful risk-benefit assessment is therefore crucial before initiating therapy. Thromboembolic disease involves syndromes of both the venous and arterial circulation, and its pathogenesis is best understood by considering the elements of Virchow's Triad. This model defines the risk factors for venous thromboembolism and allows us to classify surgical and medical patients into low, moderate and high risk groups. Similar analysis allows risk assessment for patients prone to cardiogenic embolism resulting from nonvalvular atrial fibrillation, ischaemic heart disease, rheumatic heart disease and valvular prostheses. All anticoagulant therapy is prophylactic. Primary prophylaxis involves instituting anticoagulant therapy in patients at risk, before thromboembolism occurs, while secondary prophylaxis involves treating patients with established disease. The 2 major anticoagulants, heparin and warfarin, differ in their mechanism of action, mode of administration and methods of monitoring. Either may be used as primary or secondary prophylaxis. Heparin, because it acts immediately, is the drug of choice for the short term treatment of thromboembolic disease. Warfarin is the drug of choice for long term oral maintenance therapy. The principal complication of heparin therapy is haemorrhage, although thrombocytopenia and osteoporosis may also occur; the complications of warfarin include haemorrhage and skin necrosis. The risks of complications vary with the underlying thromboembolic disease. After the benefits of treatment are weighed against the risks of complications, recommendations for therapy can be established. The use of anticoagulants in pregnancy is especially complex. Here heparin is probably the preferred agent since, unlike warfarin, it does not cross the placenta and is nonteratogenic.


Network pharmacology and experimental validation to reveal the target of matrine against PRRSV.
Porcine reproductive and respiratory syndrome (PRRS) is an epidemic animal infectious disease worldwide. In our previous research it was suggested that matrine could inhibit PRRSV infection both in vitro and in vivo, but the antiviral mechanisms are still undecided. Network pharmacology can well solve the difficult problem of "multiple targets, multiple pathways" in the research of TCM action targets. The results of network pharmacology indicated that matrine exerts its anti-PRRSV effect by targeting HSPA8 and HSP90AB1. The results of real-time fluorescent quantitative PCR and western blot showed that infection with PRRSV induced a significant increase in the expression of HSPA8 and HSP90AB1 whereas matrine treatment could significantly reverse it, and the number of viruses of PRRSV also decreased. In this study, the method of network pharmacology was used to explore HSPA8 and HSP90AB1 which were the potential targets of matrine against PRRSV on Marc-145 cells.


Cdk5 links with DNA damage response and cancer.
As an atypical member of cyclin dependent kinase family, Cyclin dependent kinase 5 (Cdk5) is considered as a neuron-specific kinase in the past decade due to the abundant existence of its activator p35 in post-mitotic neurons. Recent studies show that Cdk5 participates in a series of biological and pathological processes in non-neuronal cells, and is generally dysregulated in various cancer cells. The inhibition or knockdown of Cdk5 has been proven to play an anti-cancer role through various mechanisms, and can synergize the killing effect of chemotherapeutics. DNA damage response (DDR) is a series of regulatory events including DNA damage, cell-cycle arrest, regulation of DNA replication, and repair or bypass of DNA damage to ensure the maintenance of genomic stability and cell viability. Here we describe the regulatory mechanisms of Cdk5, its controversial roles in apoptosis and focus on its links to DDR and cancer.


Factors influencing voluntary premarital medical examination in Zhejiang province, China: a culturally-tailored health behavioral model analysis.
Premarital medical examination (PME) compliance rate has dropped drastically since it became voluntary in China in 2003. This study aimed to establish a prediction model to be a theoretic framework for analyzing factors affecting PME compliance in Zhejiang province, China. A culturally-tailored health behavioral model combining the Health Behavioral Model (HBM) and the Theory of Reasoned Action (TRA) was established to analyze the data from a cross-sectional questionnaire survey (n = 2,572) using the intercept method at the county marriage registration office in 12 counties from Zhejiang in 2010. Participants were grouped by high (n = 1,795) and low (n = 777) social desirability responding tendency (SDRT) by Marlowe-Crowne Social Desirability Scale (MCSDS). A structural equation modeling (SEM) was conducted to evaluate behavioral determinants for their influences on PME compliance in both high and low SDRT groups. 69.8% of the participants had high SDRT and tended to overly report benefits and underreport barriers, which may affect prediction accuracy on PME participation. In the low SDRT group, the prediction model showed the most influencing factor on PME compliance was behavioral intention, with standardized structural coefficients (SSCs) being 0.75 (P < 0.01), and the intention was positively determined by individual's attitude toward PME (SSCs = 0.48, P < 0.01) and subjective norms (SSCs = 0.22, P < 0.01) and negatively determined by perceived threat (SSCs = -0.08, P = 0.028). Attitudes and subjective norms were more crucial predictors for PME compliance than perceived threat (SSCs = 0.36, 0.269, and -0.06, respectively). County environmental factors played a role in PME compliance while less influential than behavioral determinates (16% vs. 84% in across factor variance partition coefficient). PME compliance might be influenced by demographic, behavioral, and social environmental factors. The verified prediction model was tested to be an effective theoretic framework for the prediction of factors affecting voluntary PME compliance. It also should be noted that internationally available behavioral theories and models need to be culturally tailored to adapt to particular populations. This study has provided new insights for establishing a theoretical model to understand health behaviors in China.


How clinical development can, and should, inform translational science.
There is an urgent need for preclinical translational efforts to be realized as breakthroughs in therapy for the many patients with life-altering conditions affecting the CNS. Despite intensive efforts, few transformative therapies have emerged, and many new potential therapies that looked promising in preclinical development have failed in the clinic. In this Perspective, we suggest that if preclinical scientists partner early with clinical scientists, they can begin to envision the pathway forward for their work through clinical trials. Options might include determining the populations to be treated, issues of dose selection, timing of intervention, duration of intervention, and the availability of biomarkers. In addition, understanding other factors that impact the likelihood that a proof-of-concept trial can be performed, as well as other critical issues, will altogether increase the attractiveness of the project to investors and partners and will also increase the likelihood that the intervention will succeed in the clinic.


Proton beam therapy for iris melanomas.
To describe the results in terms of local control, eye preservation and systemic evolution of iris melanomas treated by proton beam irradiation. Retrospective review of the charts of patients with iris melanoma treated by proton beam therapy between April 1998 and September 2002. Ciliary body melanomas with iris involvement or tumours with extrascleral invasion were excluded. Treatment consisted of 60 Gy of proton beam irradiation delivered in four fractions to the tumour volume. A total of 21 patients were treated, median follow-up of 33 months (8-72 months). 15 patients presented a lesion with documented growth. The median clinical diameter was 5 mm (2-8 mm), the median ultrasound diameter 4.8 mm (2-7.7 mm) The patients were 6% T1, 57.1% T2, and 14.3% T3 all N0M0. The iridocorneal angle was invaded by the tumour in 71.4% of patients. At the end of follow-up, all patients were alive with no proven metastatic disease except one patient with suspicious liver lesions. None of the patients showed tumour progression or ocular relapse. The tumour response at 2 years was a flat lesion for 6.3% of cases, partial regression in 75% and stable in 18.8%. None of the patients required secondary enucleation. The main complication was cataract (45% within 24 months of treatment). Raised intraocular pressure was observed in 15% of patients but no neovascular glaucoma. Proton beam therapy shows potential utility for selected cases of localised iris melanomas allowing excellent local tumour control and eye preservation. Further follow-up on larger series is needed to confirm these results.


The development of a new basic treatment equivalent model to assess linear accelerator throughput.
The basic treatment equivalent (BTE) model was developed in 1996 in an attempt to improve the measurement of linear accelerator throughput in radiotherapy. This study aimed to assess the effect of treatment set-up and patient characteristics on fraction duration, to update the BTE model and to determine the better throughput measure between fields per hour and BTE per hour. Stopwatch measurements of the duration of each radiotherapy treatment fraction delivered on each linear accelerator in participating New South Wales radiation oncology departments over a 5-day period in 2003 were undertaken. Patient, equipment and staff data were collected to assess the effect of these variables on fraction duration. A new BTE equation was derived, including the most significant variables. Statistical comparison of fields and BTE per unit time was made to assess the better predictor of fraction duration. Data collected on 27 linear accelerators in 13 departments included a total of 135 days of linear accelerator operation, 4316 fractions and 12 892 treatment fields. Seventeen factors significantly influenced fraction duration (P < 0.01). These accounted for 46% of the total variance in the models. The eight most influential predictors of prolonged fraction duration were included in the BTE model. These were as follows: high number of fields, high number of port films/electronic portal imaging, absence of automatic field-sequencing and multi-leaf collimation, high number of junctions, use of bolus and first fraction of a treatment course. The BTE per hour was shown to be a better predictor of throughput than fields per hour. The BTE model is a better measure of linear accelerator throughput. It incorporates weightings for treatment and patient factors that significantly influenced fraction duration. This measure could be routinely collected by the radiation oncology departments and included in the electronic radiotherapy information systems.


Mutations in the iduronate-2-sulfatase gene in five Norwegians with Hunter syndrome.
We have identified the mutations in the iduronate-2-sulfatase (IDS) gene of five unrelated Norwegians with Hunter syndrome by reverse transcription-polymerase chain reaction (RT-PCR) analysis of IDS mRNA followed by single strand conformation polymorphism (SSCP) analysis and cDNA sequencing. One patient had a 5-bp deletion, located at the intron 5/exon 6 junction, that created a new alternative splice site. This expanded the deletion to 9 bp in mRNA, an in-frame deletion of the first 3 codons of exon 6 of the IDS gene. In two patients point mutations were identified, the S333L mutation, which has been reported previously, and A346D (a C-->A transversion at nucleotide 1161/exon 8), which is novel. Two patients had large 3' mRNA rearrangements. The A346D mutation was associated with the mild phenotype, all others with the severe form.


Changes in ocular wavefront aberrations and retinal image quality with objective accommodation.
To evaluate changes in ocular wavefront aberrations and retinal image quality with objective accommodation in normal human eyes. Department of Ophthalmology and Visual Science, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea. Cohort study. Healthy emmetropic eyes were measured with an iTrace wavefront aberrometer while the subjects fixated at far (6.0 m) and near (40 cm). Wavefront data were analyzed with 3.0 mm and 5.0 mm pupil diameters. The influence of higher-order aberrations (HOAs) on retinal image quality was simulated by computing the modulation transfer function (MTF) from the wavefront aberrations. Eighty-two eyes of 42 subjects were evaluated. The root mean square values of total HOAs before and after accommodation with 5.0 mm pupils were statistically significantly different (P=.021). In particular, total spherical aberrations became more negative with accommodation, and the difference was statistically significant with 3.0 mm and 5.0 mm pupils (both P<.001). The MTF curves were significantly different before and after accommodation at 5 cycles per degree (cpd) and 10 cpd with 5.0 mm pupils (P=.031 and P=.045, respectively). Ocular wavefront aberrations and retinal image quality changed with accommodation in normal human eyes. Total spherical aberration changed more than other HOAs with accommodation.


LncRNA CRNDE promotes the progression and angiogenesis of pancreatic cancer via miR-451a/CDKN2D axis.
The lncRNA colorectal neoplasia differentially expressed (lncRNA CRNDE) has been reported to play a pivotal role in various cancers. However, the expression and function of CRNDE in pancreatic cancer remain unclear. The objective of this study was to investigate the effects of CRNDE on pancreatic cancer and the underlying mechanisms. The expression of CRNDE in pancreatic cancer tissues and cell lines was determined by RT-qPCR. Proliferation and angiogenesis were detected by MTT, colony formation, transwell and tube formation assays in vitro and in vivo. ELISA assay was used to detect the secretion of VEGFA. IHC was performed to test the expression levels of Ki67 and CD31. The binding sites between CRNDE, CDKN2D and miR-451a were predicted by bioinformatics analysis. Dual luciferase reporter and RNA immunoprecipitation assays were conducted to confirm the interaction with each other. The results showed that CRNDE was significantly up-regulated in pancreatic cancer tissues as well as cell lines. CRNDE overexpression promoted the progression and angiogenesis of pancreatic cancer cells in vitro and in vivo. Moreover, we identified that CRNDE functioned as a sponge for miR-451a and CRNDE overexpression inhibited the expression of miR-451a. Furthermore, we confirmed that miR-451a directly interacted with CDKN2D and negatively regulated CDKN2D expression. In addition, CRNDE was found to positively regulate CDKN2D expression and mediate pancreatic cancer cell proliferation and angiogenesis through miR-451a/CDKN2D axis. CRNDE modulates cell proliferation and angiogenesis via miR-451a/CDKN2D axis in pancreatic cancer, which provides a potential therapeutic target for pancreatic cancer treatment.


Functions of ephrin/Eph interactions in the development of the nervous system: emphasis on the hippocampal system.
Ephrins and their Eph receptors are membrane-anchored proteins that have key roles in the development of the Central Nervous System. The main characteristics of ephrin/Eph interactions are that their effect is mediated by cell-to-cell contacts and that they can propagate bidirectional signals downstream of the ligand-receptor complex. These characteristics make ephrins and Eph receptors critical cues in the regulation of migrating cells or axons, and in the establishment of tissue patterns and topographic maps in distinct regions of the developing brain. In addition, ephrins and Eph receptors regulate synapse formation and plasticity. These roles would be promoted by complementary gradual expression of receptors and ligands in the neurons involved. Although, historically, ephrins and Eph receptors have been considered as repulsion signals through barriers or gradients, new evidence indicates that they may be both inhibitory and permissive/active cues depending on expression levels. The expression of distinct ligands and receptors in the developing and mature hippocampus suggests that these proteins are involved in distinct processes during the development and maturation of the hippocampal region. In fact, recent studies have shown that ephrin/Eph signaling participates in the formation of the layer-specific patterns of hippocampal afferents, in synaptogenesis and in plasticity. Therefore, ephrin/Eph interactions should be considered a crucial system in the development and maturation of the brain regions, including the hippocampus.


Identification of prognostic factors in patients with cervical cancer and supraclavicular lymph node recurrence.
Patients with cervical cancer and supraclavicular lymph nodes (SLN) recurrence have a poor but heterogeneous prognosis. The aim of this study was to identify potential prognostic factors - including FDG-PET results - that may affect survival and treatment outcomes in patients with this group of patients. Between January 2001 and December 2008, we identified a total of 31 consecutive patients with cervical cancer who had evidence of SLN recurrence. All participants underwent FDG-PET. Survival was measured from the date of documented SLN recurrence. The latency period was defined as the length of time from the date of first diagnosis to the date of SLN recurrence. The median follow-up time was 22.8 months (range: 4.7-105.1). The 3- and 5-year survival rates were 41% and 27.3%, respectively. Patients with intermediate SUV values (between 4.3 and 8) had a significantly better prognosis than subjects with both high (>8) or low (<4.3) SUV values (p=0.004). Latency period <2 years, SCC-Ag levels ≥ 4ng/mL, recurrence extend beyond SLN, and SUV of <4.3 >8 were significant adverse prognostic factors by multivariate analysis. The 3-year overall survival (OS) rate of patients carrying 0-1 adverse prognostic factors was 90% (low-risk group), while 3-year OS rates for intermediate-risk group (2 factors) and high-risk group (3-4 factors) were 30% and 0%, respectively (p=0.001). Our results justify the use of PET (accurate extent of relapse and SUV) as a prognostic tool in patients with cervical cancer and SLN recurrence.


Comparison of healthcare utilization and life-sustaining interventions between patients with glioblastoma receiving palliative care or not: A population-based study.
Palliative care has historically been under-utilized in patients with glioblastoma. Furthermore, literature on the utilization of healthcare and life-sustaining interventions during the late-stage of glioblastoma has been limited. To identify and compare healthcare utilization and life-sustaining interventions between patients with glioblastoma who received palliative care and who did not based on patients identified retrospectively from Taiwan Cancer Registry between January 2007 and December 2017. In this study, palliative care was defined on the basis of claims submitted to the National Health Insurance, which has a specific code for it. Variables included demographic characteristics, the utilization of healthcare services, and invasive life-sustaining interventions. Of the 1994 patients with glioblastoma identified, 1784 fulfilled the inclusion criteria, 613 (34%) of whom received palliative care. The survival of patients with glioblastoma under palliative care was significantly longer than that of those without palliative care. Those without palliative care had significantly more frequent intensive care unit admissions and a longer cumulative length of intensive care unit stay. Regarding cardiopulmonary or respiratory treatments, patients without palliative care had significantly more invasive interventions than those with palliative care. Patients receiving palliative care had significantly lower odds than those without life-sustaining interventions. Our retrospective analysis reveals that glioblastoma patients without palliative care had greater odds of receiving life-sustaining treatments within 1 year before their death, although no gains in survival as compared to those that received palliative care. These findings highlight the urgent need for palliative care in caring for patients with glioblastoma.


A simplified technique for botulinum toxin injections in children with neurogenic bladder.
Botulinum toxin type A has revolutionized the treatment of neurogenic bladder dysfunction. The original injection technique used a rigid cystoscope and a flexible collagen needle. To date botulinum toxin type A injection techniques have not been standardized. We present our experience in pediatric patients using a new flexible injection system. We treated 24 patients 3.8 to 17.5 years old who had neurogenic bladder dysfunction with botulinum toxin type A bladder and/or sphincter injection using a rigid cystoscope and the new N-DO™ endo-injector needle system. Another 24 patients 3.6 to 17.8 years old were treated with a 3.7Fr standard flexible needle and served as controls. Operative time, hospital stay, complications and efficacy were considered. Selection criteria and treatment were the same in the 2 groups. The 10 IU/kg dose was determined according to European Association of Urology guidelines. All patients received botulinum toxin type A bladder injection while 11 patients in the endo-injector group and 5 controls also received urethral injection. In the endo-injector needle and control groups average operative time was 12.4 and 17.3 minutes for the bladder, and 5.1 and 10.1 minutes for the urethra, respectively (each p <0.05). All patients were discharged home the day after the procedure. No complications were observed. Urodynamics revealed an average maximum detrusor pressure decrease of 25 and 21 cm H(2)O, and an average bladder capacity increase of 75 and 80 ml in the endo-injector and control groups, respectively (p not significant). While retaining efficacy, the endo-injector needle technique appears to be more rapid than the standard procedure for botulinum toxin type A injection for neurogenic bladder dysfunction. Whether patients may be treated with sedation only remains to be clarified.


Association between smoking and post-load plasma glucose levels using a 75-g oral glucose tolerance test: the Saku Study.
Current smoking was associated with low insulin secretion and high 30-min plasma glucose (PG), 60-min PG, and area under the curve of PG, whereas current smoking was not associated with fasting PG and 2-h PG levels in both individuals with normoglycemia and individuals with pre-diabetes in a large-scale community-based study.


A New Shifting Strategy in Flashing Light Based on the Cell Growth Curve to Enhance β-carotene Biosynthesis in Dunaliella salina.
Microalgae Dunaliella salina has been recognized as an effective source of β-carotene. To elevate the productivity of this species, light has been served as an important induction factor, in this regard, a new idea was inspired as designing a red-to-blue wavelength shifting system based on the growth rate and cell behavior. A photobioreactor was exposed to two panels of flashing red and blue LEDs. At the commencement of the stationary phase, the wavelength shifting was applied and red LEDs were replaced with blue ones. Maximum β-carotene content of 10 mg.g-1 was obtained; at least 300% higher than the content in the controlled system (flashing red and blue light to the end of growth).


Rubella outbreak in a prenatal clinic: management and prevention.
An obstetrician and two staff members developed rubella and exposed 56 susceptible pregnant women in a large prenatal and family planning clinic. Two women (3.6%) developed rubella at 27 and 38 weeks' gestation and delivered uneventfully. Sixteen hundred clinic and hospital employees were tested, with 79% of the total and 48 of 59 (81.4%) OB/GYN personnel showing prior infection and/or immunity (HAI titer greater than or equal to 1:8). Of those susceptible, all obstetrical and most other personnel were vaccinated and removed from high risk areas until immune. Our management of a rubella outbreak and recommendations on hospital and clinic policy to avoid potential health problems are discussed.


Bariatric and metabolic surgery during COVID-19 outbreak phase 2 in Italy: why, when and how to restart.
In Italy elective bariatric and metabolic surgery was cancelled on February 21,2020 at the beginning of the so-called phase 1 of the SARS-CoV-2 outbreak. Gradually it was restarted on May 4,2020 at the beginning of the so-called phase 2, when epidemiological data showed containment of the infection. Before the outbreak in eight high-volume bariatric centers 840 patients were surgically treated developing a Covid-19 infection, during phase 1, in only 5 cases (0.6%) without mortality. The post-operative complication rate was similar when compared to the 836 subjects submitted to bariatric surgery the year before. Since the high prevalence of infection in subjects with BMI > 30, it was argued that early intervention on obesity during phase 2 could help to minimize the effects of the disease in the event of a possible reversion to a SARS-CoV-2 outbreak phase 1. At the same time a prospective observational study from July 1 till the WHO declaration of the end of the pandemic has started in the eight high volume centers to monitor the post-operative outcome and its effect on SARS-CoV-2 infection.


Percutaneous nephrostomy versus indwelling ureteral stents in patients with bilateral nongenitourinary malignant extrinsic obstruction.
We present five cases of bilateral extrinsic ureteral obstruction in advanced nongenitourinary abdominal malignancy. They show the superiority of percutaneous nephrostomy to indwelling ureteral stents in providing diversion. We suggest that percutaneous nephrostomy drainage should be the management of choice in extrinsic obstruction by advanced abdominal malignancies.


The advantages of titanium alloy over stainless steel plates for the internal fixation of fractures. An experimental study in dogs.
An experimental study is reported of fracture healing in the femora of 36 Beagle dogs, comparing the results of using stainless steel plates with those of using less rigid titanium alloy plates. The alloy plates led to the appearance of a small amount of periosteal callus without any histological evidence of fracture instability, thus allowing the radiological assessment of fracture union. This also produced less bone loss during the remodelling phase. Radiological measurements 24 weeks after osteotomy showed cortical thickness to be reduced by six per cent under titanium alloy and by 19 per cent under stainless steel, while histological measurements showed a total bone loss of 3.7 per cent under titanium alloy and of 11 per cent under stainless steel plates. Removal of the titanium alloy plates after eight weeks followed by a recovery period of 16 weeks produced an increase of cortical thickness of 69 per cent and a gain in total bone mass of 30 per cent. Titanium alloy plates also produced less soft-tissue reaction than stainless steel plates. It is concluded that this alloy is a promising material for internal fixation devices.


Safety and efficacy of endoscopic ultrasound-guided gallbladder drainage combined with endoscopic retrograde cholangiopancreatography in the same session.
Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) is an emerging option for acute cholecystitis in non-surgical candidates. Combining endoscopic retrograde cholangiopancreatography (ERCP) for common bile duct stones with EUS-GBD in a single session might become a non-surgical management strategy to comprehensively treat gallstone disease in selected patients. Single-center retrospective cohort study comparing outcomes between EUS-GBD alone (group A) and single-session ERCP combined with EUS-GBD (group B). Consecutive patients who underwent EUS-GBD with a lumen-apposing metal stent (LAMS) between June 2011 and August 2018 were analyzed. Exclusion criteria were subjects included in randomized clinical trials, patients who had had ERCP within 5 days of EUS-GBD, patients in whom ERCP or EUS-GBD was carried out for salvage of one or the other procedure, and patients who underwent concurrent EUS-guided biliary drainage. One hundred and nine consecutive patients underwent EUS-GBD with LAMS during the study period. Seventy-one patients satisfied the inclusion criteria and 34 patients were in group A and 37 in group B. Baseline characteristics were similar in both groups. There were no significant differences in technical (97.1% vs 97.3%; P = 0.19) and clinical success rates (88.2% vs 94.6%; P = 0.42) of EUS-GBD in group A versus group B. Rate of adverse events was similar in both groups, five (14.7%) in group A versus five (13.5%) in group B. Single-session EUS-GBD combined with ERCP has comparable rates of technical and clinical success to EUS-GBD alone. A combined EUS-GBD and ERCP procedure does not appear to increase adverse events and makes possible comprehensive treatment of gallstone disease by purely endoscopic means.


Control of membrane barrier during bacterial type-III protein secretion.
Type-III secretion systems (T3SSs) of the bacterial flagellum and the evolutionarily related injectisome are capable of translocating proteins with a remarkable speed of several thousand amino acids per second. Here, we investigate how T3SSs are able to transport proteins at such a high rate while preventing the leakage of small molecules. Our mutational and evolutionary analyses demonstrate that an ensemble of conserved methionine residues at the cytoplasmic side of the T3SS channel create a deformable gasket (M-gasket) around fast-moving substrates undergoing export. The unique physicochemical features of the M-gasket are crucial to preserve the membrane barrier, to accommodate local conformational changes during active secretion, and to maintain stability of the secretion pore in cooperation with a plug domain (R-plug) and a network of salt-bridges. The conservation of the M-gasket, R-plug, and salt-bridge network suggests a universal mechanism by which the membrane integrity is maintained during high-speed protein translocation in all T3SSs.


Characterizing the structure and photocycle of PR 2D crystals with CD and FTIR spectroscopy.
We present here a study on proteorhodopsin (PR) 2D crystals with analytical ultracentrifugation, circular dichroism and Fourier transform infrared (FTIR) spectroscopy. The aim of our experiments was to test the activity of 2D crystal sample preparations and to gain further insight in PR structure, stability and function with these techniques. Our results demonstrate higher stability compared to detergent-solubilized or reconstituted samples. For different pH values, low pH 2D crystals tend to form bigger aggregates and are less stable than at basic pH. The pH 9 sample shows a sharp phase transition during heat denaturation and there is also evidence for protein-protein interaction due to the close proximity of the proteins in the 2D crystals. In the FTIR measurements at cryogenic temperatures (77 K), we characterized the first step in the PR photocycle. At pH 9, the K intermediate could be observed and the samples showed no orientation effects. At pH 5, we could trap the K/L intermediate, characterized by its negative IR signal at 1741 cm(-1). In rapid-scan FTIR experiments, we could also identify the M intermediate of the photocycle at basic pH. We conclude that the PR 2D crystals exhibit a fully functional photocycle and are therefore well suited for further studies on the proton transport mechanism of PR.


Role of interleukin 1 in mycoplasma mitogen-induced proliferation of human T cells.
Recently, a mitogenic effect of the supernatant of cultured mycoplasma arthritidis (MAS) on human and murine lymphocytes has been described. Here, we studied the role of accessory cells (AC) in MAS-induced T cell proliferation in a system of human leukocytes. Nylon-wool purified T cells were non-responsive to MAS with regard to both proliferation and IFN-gamma production. The capacity of T lymphocytes to respond to MAS could be restored when viable AC were added. Treatment of AC with UV light resulted in a cell population which was incapable of reconstituting T cells. Addition of human recombinant interleukin 1 alpha (IL 1 alpha) or IL 1 beta again showed a reconstituting effect. However, only a partial reconstitution of the T cell response could be achieved by addition of recombinant IL 1 alpha or IL 1 beta. The optimal restoration was achieved by adding IL 1 at a concentration of 100 U/ml IL 1 alpha or 100 U/ml IL 1 beta. The results indicate that metabolically active AC were required for MAS-induced T cell proliferation to occur and that IL 1 was able to substitute for the role of AC. Since this restoration was only partial, it remains to be determined whether factors others than IL 1 are required to fully substitute the role of accessory cells.


Prevalence and molecular characterization of Giardia duodenalis from sheep in central Italy.
Giardiosis in domestic ruminants is an important parasitic disease and it has been shown to impair growth in lambs, thus constituting a disease of economic concern. In Europe, surveys on the prevalence of giardiosis in sheep are limited. In order to obtain additional information on the presence of giardiosis and on the potential zoonotic role of Giardia duodenalis affecting sheep in central Italy, faecal samples of 325 native sheep from 20 farms in Abruzzo region (Italy) were examined for the presence of Giardia and the isolates were genotyped and sequenced. G. duodenalis cysts were detected in five of the 325 sheep (1.5%) (mean of 450 cysts/g) coming from two farms. The 770-bp fragment of the glutamate dehydrogenase gene and the 753-bp fragment of the beta-giardin gene showed 100% homology with the Assemblage AI. This work suggests for the first time in Italy that sheep carry a Giardia genotype, which can be a potential public health hazard.


The origin and spread of human leukemia.
The human leukemias are a group of hematologic neoplasms characterized by uncontrolled proliferation of cells concerned with blood cell production. The cause(s) of human leukemia remains unknown. Bone marrow (BM) is believed to be the site of origin of human leukemias, although the specific locus(i) and/or cell(s) from which it arises have not been definitively identified. Generally, human leukemias and related proliferative diseases are thought to be clonal in nature; affecting a single hematopoietic stem cell, which then proliferates and replaces the marrow of normal hematopoietic stem cell systems. The condition is believed to be malignant in nature. Results of our current morphologic studies on well-fixed, ideally-stained thin sections of plastic-embedded bone marrow biopsies (BMB) from a large number of acute (AML, ALL) and chronic (CGL, CLL) leukemia patients suggest that human leukemias may not be clonal diseases. Instead, a large population of other resident cells--'endosteal cells'--appears to become involved in the process and it is possible that all members of this group enter the activity simultaneously. This change (transformation) in the endosteal cell population might be due to an abnormality (qualitative or quantitative) of diffusable, humoral factors (yet to be identified) that are responsible for the growth and proliferation of these hematopoietic precursor cells. In this context, the human leukemias may be considered not as malignant, but rather the result of an aberration of factor(s) that control hematopoiesis. In this respect, the human leukemias, particularly AML, ALL and CML, might be analogous to pernicious anemia (megaloblastic anemia) as it was understood 40-50 years ago.(ABSTRACT TRUNCATED AT 250 WORDS)


Effects of nephrotoxic compounds on active uptake of drugs in isolated renal tubules in rabbits.
The uptake of sulfonamides and phenolsulfonphthalein (PSP) was examined in vitro using isolated renal proximal tubule suspension, and the effects of nephrotoxic compounds on the uptake of sulfamethizole (SMZ) were studied. The uptake of SMZ and PSP was energy dependent and was inhibited competitively by iodopyracet (IP), which is transported actively by the p-aminohippurate mechanism. The uptake of sulfamethoxazole was also reduced by IP but that of sulfanilamide was negligible. The present results correspond well with those of in vitro experiments reported previously. Nephrotoxic compounds, mercuric chloride, neomycin, viomycin and kanamycin, decreased the uptake of SMZ non-competitively. The inhibitory action of the three antibiotics corresponds with in vivo potency, suggesting that this renal tubule preparation may provide a simple method for predicting the nephrotoxicity of drugs.


A comparative characterization study between fungal and bacterial eumelanin pigments.
Melanins are the most common and the most enigmatic natural pigments in the nature that found in many different taxa group such as bacteria, yeasts, fungi, insects, plants, reptiles, birds and mammals. These biological macromolecules are highly complex cross-linked, heterogeneous biopolymers and composed of polymerized phenolic and/or indolic compounds. Recently, interest in these ubiquitous biopolymers has been increasing considerably in many different areas such as medicine, pharmacology, cosmetics, organic electronic and optoelectronics because of their versatile properties. In this study, four different extracellular eumelanin pigments (two bacterial eumelanins and two fungal eumelanins) were characterized by different spectrometric techniques such as FT-IR, XRD, NMR and UV-vis. In XRD analyzes, purified fungal and bacterial eumelanin pigments were characterized by giving a wide peak at about 22o with an angle of 2θ. Furthermore, in the 1 H NMR spectra of these biopolymers, it was observed that all pigments have signals in both aromatic and aliphatic regions. In addition to these analyzes, nanostructures of these biopolymers were characterized using atomic force microscopy (AFM) and scanning electron microscopy (SEM). Finally, eumelanin pigment producer microorganisms were molecularly characterized. 16 S rDNA and 18 S rDNA sequence analysis results of these microorganisms (Streptomyces fulvissimus MPPS4, Streptomyces xiamenensis MPPS6, Aspergillus niger MPPF16 and Aspergillus terreus MPPF25) were deposited in NCBI GenBank® database with accession number MT825594, MT973972, MW652652 and MW652653 respectively. The online version contains supplementary material available at 10.1007/s12088-022-01012-1.


Comparative analysis of singer's high formant in different type of singing voices.
The presence of singer's high formant (SHF) in singers of different musical styles was investigated. The voices of 10 opera, 8 folk, 4 pop singers and 53 (non-singing) controls were recorded. The vowel 'a' was sung in three different registers. The percent of energy in the range of SHF and the stability of the pitch period generation were evaluated. The signals of all the singers are characterized by very high stability of the pitch period generation (> 99%), but their formant structures differ considerably. Energy concentration in the range of SHF is 23, 16, 7 and < 4% for opera, folk and pop singers and the controls, respectively.


β-1 and β-2 adrenergic receptor polymorphism and association with cardiovascular response to orthostatic screening.
Variation in the beta-1 and beta-2 adrenergic receptor genes (ADRB1 and ADRB2, respectively) may influence cardiovascular reactivity including orthostatic stress. We tested this hypothesis in a head-up tilt (HUT) screening protocol in healthy young adults without history of syncope. Following brachial arterial catheter insertion, 120 subjects (age 18-40, 72 females, Caucasian) underwent 5min 60° HUT. Polymorphisms tested were: Ser49/Gly and Arg389/Gly in ADRB1; and Arg16/Gly, Gln27/Glu, and Thr164/Ile in ADRB2. Three statistical models (recessive, dominant, additive) were evaluated using general linear models with analysis for each physiologic variable. A recessive model demonstrated a significant association between Arg16/Gly and: absolute supine and upright HR; HUT-induced change in cardiac index (CI), stroke index (SI) and systemic vascular resistance (SVR); and supine and upright norepinephrine values. Blood pressure was not influenced by genotype. Fewer associations were present for other polymorphisms: Ser49/Gly and the change in SI (dominant model), and Arg389/Gly and supine and HUT norepinephrine (additive model). We conclude that in this population, there is a robust association between Arg16/Gly and HUT responses, such that 2 copies of Arg16 increase supine and upright HR, and greater HUT-induced decreases in CI and SI, with greater increases in SVR and norepinephrine. ADRB1 gene variation appears to impact SI and plasma NE levels but not HR. Whether ADRB2 gene variation is ultimately disease-causing or disease-modifying, this study suggests an association between Arg16/Gly and postural hemodynamics, with sympathetic noradrenergic activity affected in a similar direction. This may have implications in the development of orthostatic disorders.


Complete resection of pure anterior foramen magnum meningioma without neurovascular injuries poses a big challenge: Case report.
Meningiomas are common neoplasms representing 14.3-19% of all intracranial tumors. Among all the meningiomas, only 1.8-3.2% arises at the foramen magnum (FM) level.Most of the lesions (68%-98%) arising anterolaterally, followed by postolateral, purely posterior and, more rarely, purely anterior. We report a case of A 42-year-old female presented with a history of neck pain with progressive spastic hemiparesis. MRI revealed well-defied pure anterior and on both sides of vertebral artery, foramen magnum lesion. Through conservative transcondylar approach, Lesion was removed totally in a piecemeal fashion. Histopathology revealed meningothelial meningioma. The patient had a dramatic recovery. The exposure allowed by the far-lateral retrocondylar or partial transcondylar approach is adequate for resecting even anterior intradural FMMs.Reports about Foramen magnum meningioma aren't common, but reports on pure anterior foramen magnum meningioma are very rare. The prerequisite for treating FM meningiomas (FMMs) is the perfect knowledge of the surgical anatomy. The opportunity to give the patient a symptom-free and normal life should not be missed in such cases.


Extremely rapid and reversible optogenetic perturbation of nuclear proteins in living embryos.
Many developmental regulators have complex and context-specific roles in different tissues and stages, making the dissection of their function extremely challenging. As regulatory processes often occur within minutes, perturbation methods that match these dynamics are needed. Here, we present the improved light-inducible nuclear export system (iLEXY), an optogenetic loss-of-function approach that triggers translocation of proteins from the nucleus to the cytoplasm. By introducing a series of mutations, we substantially increased LEXY's efficiency and generated variants with different recovery times. iLEXY enables rapid (t1/2 < 30 s), efficient, and reversible nuclear protein depletion in embryos, and is generalizable to proteins of diverse sizes and functions. Applying iLEXY to the Drosophila master regulator Twist, we phenocopy loss-of-function mutants, precisely map the Twist-sensitive embryonic stages, and investigate the effects of timed Twist depletions. Our results demonstrate the power of iLEXY to dissect the function of pleiotropic factors during embryogenesis with unprecedented temporal precision.


Memory of the initial conditions in an incompletely chaotic quantum system: universal predictions with application to cold atoms.
Two zero-range-interacting atoms in a circular, transversely harmonic waveguide are used as a test bench for a quantitative description of the crossover between integrability and chaos in a quantum system with no selection rules. For such systems we show that the expectation value after relaxation of a generic observable is given by a linear interpolation between its initial and thermal expectation values. The variable of this interpolation is universal; it governs this simple law to cover the whole spectrum of the chaotic behavior from integrable regime through the well-developed quantum chaos. The predictions are confirmed for the waveguide system, where the mode occupations and the trapping energy were used as the observables of interest; a variety of the initial states and a full range of the interaction strengths have been tested.


Dramatic nucleolar dispersion in the salivary gland of Schwenkfeldina sp. (Diptera: Sciaridae).
Micronucleoli are among the structures composing the peculiar scenario of the nucleolus in salivary gland nuclei of dipterans representative of Sciaridae. Micronucleolar bodies contain ribosomal DNA and RNA, are transcriptionally active and may appear free in the nucleoplasm or associated with specific chromosome regions in salivary gland nuclei. This report deals with an extreme case of nucleolar fragmentation/dispersion detected in the salivary gland of Schwenkfeldina sp. Such a phenomenon in this species was found to be restricted to cell types undergoing polyteny and seems to be differentially controlled according to the cell type. Furthermore, transcriptional activity was detected in virtually all the micronucleolar bodies generated in the salivary gland. The relative proportion of the rDNA in polytene and diploid tissues showed that rDNA under-replication did not occur in polytene nuclei suggesting that the nucleolar and concomitant rDNA dispersion in Schwenkfeldina sp. may reflect a previously hypothesised process in order to counterbalance the rDNA loss due to the under-replication. The chromosomal distribution of epigenetic markers for the heterochromatin agreed with early cytological observations in this species suggesting that heterochromatin is spread throughout the chromosome length of Schwenkfeldina sp. A comparison made with results from another sciarid species argues for a role played by the heterochromatin in the establishment of the rDNA topology in polytene nuclei of Sciaridae.


Characterization of binding sites for diisopropyl phosphorofluoridate in spinal cord cytosol.
Gel filtration chromatography was performed on cytosol preparation of hen spinal cord to find molecular target(s) for organophosphorus-induced delayed neurotoxicity (OPIDN). Three binding peaks of [(3)H]diisopropyl phosphorofluoridate (DFP), an organophosphate that induces OPIDN, were separated from the cytosol preparation. The activities of acetylcholinesterase (AChE) and neuropathy target esterase (NTE) that has been proposed as a screening method for OPIDN eluted in the fractions within these two DFP binding peaks. However, the other peak had none of the activities of AChE and NTE. Therefore, this DFP binding proteins in cytosol may be peculiar to the pathogenesis of OPIDN.


Effect of anti-adhesion barrier solution containing ciprofloxacin-hydrocortisone on abraded mucosa with otitis media.
No study to date has assessed the anti-adhesive effect of new middle ear (ME) packing agents in. This study compared the anti-inflammatory and anti-adhesive effect of antibiotic-steroid containing packing agents in abraded mucosa of the ME inflammation. Transbullar injection of a saline suspension of Pseudomonas aeruginosa lipopolysaccharide (LPS) induced otitis media. ME mucosa of guinea pigs was abraded using a pick 30 min after LPS inoculation. The animals were divided into four groups of 10 guinea pigs each. In group A, ME cavity was preserved without any packing. In group B, ME cavity was packed with soluble hyaluronic acid-carboxymethyl cellulose (HA-CMC). In group C, the ME cavity was packed with soluble HA-CMC. In group D, the ME cavity was packed with antibiotic-steroid containing soluble HA-CMC. Otoendoscopic examination, auditory brainstem responses (ABRs), and radiographic examination using computerized tomography (CT) were performed at 2 weeks post-surgery. Histopathological evaluation for ME mucosa was performed by light microscopy (LM) and scanning electron microscopy (SEM). Otoendoscopic findings and CT findings revealed that group D showed the best recovery of aeration in the ME compared to other groups. Recovery of ABRs threshold was significantly attenuated in group D. In LM and SEM findings, group D showed normalized mucosal thickening compared to other groups. ME packing by antibiotic-steroid containing soluble HA-CMC may be useful in the abraded mucosa of the ME inflammation.


The role of adjuvant chemotherapy in stage II and III mucinous colon cancer.
Mucinous adenocarcinoma is a subtype of colonic adenocarcinoma associated with worse survival compared to nonmucinous adenocarcinoma. Prior studies on the effect of chemotherapy on survival in mucinous adenocarcinoma have shown mixed results. The aim of this study is to evaluate the effect of chemotherapy on the survival of patients with stage II and III mucinous adenocarcinoma. The National Cancer Database was used to identify patients diagnosed with stage II or III nonmucinous adenocarcinoma or mucinous adenocarcinoma between 2004 and 2016. The primary outcome was overall survival. Fourteen thousand and three hundred patients with stage II mucinous colon adenocarcinoma and 16 741 patients with stage III mucinous colon adenocarcinoma were identified. There was no significant difference in survival between nonmucinous adenocarcinoma and mucinous adenocarcinoma patients in adjusted analysis for stage II disease (HR:1.00, 95%CI:0.98-1.02, P = .99), but there was a significant difference for stage III disease (HR:1.05, 95%CI:1.03-1.07, P < .001). In propensity-matched cohorts of patients with mucinous adenocarcinoma, chemotherapy was significantly associated with survival in stage II (HR:0.79, 95%CI:0.69-0.90, P < .001) and stage III disease (HR:0.56, 95%CI:0.52-0.60, P < .001). Patients with stage II or stage III mucinous adenocarcinoma of the colon who are given adjuvant chemotherapy have significantly improved survival compared to patients not given chemotherapy.