Application of flow cytometric measurement of surface IgG in kinetic analysis of monoclonal antibody synthesis and secretion by murine hybridoma cells.
The kinetics of antibody synthesis and secretion from a murine hybridoma cell line were studied using measurements of total cell-associated IgG, surface IgG, and IgG secreted into the medium. Kinetic analysis of IgG secretion demonstrates approximately constant secretion rate per viable cell over the entire batch cultivation. A correlation was observed (r2 = 0.74) between mean surface immunofluorescence and the total cell-associated IgG determined by ELISA of detergent-extracted cell lysates. No correlation was found between specific secretion rate and mean surface IgG level estimated by immunofluorescence flow cytometry measurements. Material balances on cellular IgG demonstrated that about 7% of the antibody which was synthesized during exponential batch growth was not released to the growth medium. Distributions of single-cell surface antibody content showed two subpopulations, one with very low surface IgG. The fraction of the population with low surface IgG increased throughout a batch cultivation.


A Comparison of Risk Classification Systems of Colorectal Adenomas: A Case-Cohort Study.
Because post-polypectomy surveillance uses a growing proportion of colonoscopy capacity, more targeted surveillance is warranted. We therefore compared surveillance burden and cancer detection using 3 different adenoma classification systems. In a case-cohort study among individuals who had adenomas removed between 1993 and 2007, we included 675 individuals with colorectal cancer (cases) diagnosed a median of 5.6 years after adenoma removal and 906 randomly selected individuals (subcohort). We compared colorectal cancer incidence among high- and low-risk individuals defined according to the traditional (high-risk: diameter ≥10 mm, high-grade dysplasia, villous growth pattern, or 3 or more adenomas), European Society of Gastrointestinal Endoscopy (ESGE) 2020 (high-risk: diameter ≥10 mm, high-grade dysplasia, or 5 or more adenomas), and novel (high-risk: diameter ≥20 mm or high-grade dysplasia) classification systems. For the different classification systems, we calculated the number of individuals recommended frequent surveillance colonoscopy and estimated number of delayed cancer diagnoses. Four hundred and thirty individuals with adenomas (52.7%) were high risk based on the traditional classification, 369 (45.2%) were high risk based on the ESGE 2020 classification, and 220 (27.0%) were high risk based on the novel classification. Using the traditional, ESGE 2020, and novel classifications, the colorectal cancer incidences per 100,000 person-years were 479, 552, and 690 among high-risk individuals, and 123, 124, and 179 among low-risk individuals, respectively. Compared with the traditional classification, the number of individuals who needed frequent surveillance was reduced by 13.9% and 44.2%, respectively, and 1 (3.4%) and 7 (24.1%) cancer diagnoses were delayed using the ESGE 2020 and novel classifications. Using the ESGE 2020 and novel risk classifications will substantially reduce resources needed for colonoscopy surveillance after adenoma removal.


Determination of lead and nickel in environmental samples by flame atomic absorption spectrometry after column solid-phase extraction on Ambersorb-572 with EDTA.
Lead and nickel were preconcentrated as their ethylenediaminetetraacedic acid (EDTA) complexes from aqueous sample solutions using a column containing Ambersorb-572 and determined by flame atomic absorption spectrometry (FAAS). pH values, amount of solid phase, elution solution and flow rate of sample solution have been optimized in order to obtain quantitative recovery of the analytes. The effect of interfering ions on the recovery of the analytes has also been investigated. The recoveries of Pb and Ni under the optimum conditions were 99 +/- 2 and 97 +/- 3%, respectively, at 95% confidence level. Seventy-five-fold (using 750 mL of sample solution and 10 mL of eluent) and 50-fold (using 500 mL of sample solution and 10 mL of eluent) preconcentration was obtained for Pb and Ni, respectively. Time of analysis is about 4.5 h (for obtaining enrichment factor of 75). By applying these enrichment factors, the analytical detection limits of Pb and Ni were found as 3.65 and 1.42 ng mL(-1), respectively. The capacity of the sorbent was found as 0.17 and 0.21 mmol g(-1) for Pb and Ni, respectively. The interferences of some cations, such as Mn2+, Co2+, Fe3+, Al3+, Zn2+, Cd2+, Ca2+, Mg2+, K+ and Na+ usually present in water samples were also studied. This procedure was applied to the determination of lead and nickel in parsley, green onion, sea water and waste water samples. The accuracy of the procedure was checked by determining Pb and Ni in standard reference tea leaves sample (GBW-07605). The results demonstrated good agreement with the certified values.


Behavior of spontaneous otoacoustic emissions following intense ipsilateral acoustic stimulation.
Following presentation of brief, intense pure tones spontaneous otoacoustic emissions (SOAEs) were reduced in frequency and/or amplitude. The effects were highly tuned with exposures between 1/8 and 5/8 of an octave below the SOAE producing the maximum changes. Exposure frequencies above the SOAE had no effect. The degree of tuning observed depended upon the post-exposure time sampled, with sharpness maximal between 3 and 120 s post-exposure. The effects increased nonlinearly as exposure level and duration were increased. The recovery functions were biphasic, the first phase being rapid and non-monotonic over about 2 min, while the second phase was monotonic and slow, sometimes taking several hours. These data are consistent with changes in outer hair cell (OHC) function and support the hypothesis that OHC changes underlie behavioral temporary threshold shift (TTS).


Overweight and obesity in children with newly diagnosed inflammatory bowel disease.
Determination of overweight and obesity prevalence in children with inflammatory bowel disease (IBD) at the time of diagnosis. This was a multicenter retrospective study. The study group consisted of children with new cases of IBD diagnosed in 2005-2013 according to the Porto criteria. Hospital admission records were reviewed for demographic and clinical characteristics. BMI-for-age and gender percentile charts were used to define overweight as ≥85th BMI percentile and obesity as ≥95th BMI percentile. 675 patients were evaluated: 368 with Crohn's disease (CD) and 307 with ulcerative colitis (UC). Of these, 54.8% were boys and 45.2% were girls. There were no statistically significant differences in age, weight, height and disease activity between the CD and UC patients. The UC patients had higher BMI values than the CD patients. The prevalence of overweight and obesity was higher in the UC than the CD patients (4.89% CI95 2.76-7.93 vs. 2.45% CI95 1.12-4.59 and 8.47% CI95 5.61-12.16 vs. 1.9% CI95 0.77-3.88, respectively); the differences were statistically significant (-2.44% CI95 -5.45 to 0.49 and -6.57% CI95 -10 to -3.1, respectively). The risk of overweight/obesity was 3.5 times higher for patients with UC (OR=0.272, CI95 0.14-0.49, p=0.0004). The prevalence of overweight and obesity in newly diagnosed children with IBD was 8.4% and was higher in patients with UC than in patients with CD. The results of this study have shown that not only malnourished children may suffer from IBD but also children who are overweight or obese at the time of diagnosis.


Association between parent attitudes and receipt of human papillomavirus vaccine in adolescents.
Human papillomavirus (HPV) vaccine coverage rates remain low. This is believed to reflect parental hesitancy, but few studies have examined how changes in parents' attitudes impact HPV vaccine uptake. This study examined the association between changes in parents' vaccine attitudes and HPV vaccine receipt in their adolescent children. A baseline and 1-year follow-up survey of HPV vaccine attitudes was administered to parents of 11-17 year olds who had not completed the HPV vaccine series. Changes in attitudinal scores (barriers, harms, ineffectiveness, and uncertainties) from the Carolina HPV Immunization Attitudes and Beliefs Scale were assessed. Two outcomes were measured (in parents' adolescent children) over an 18-month period and analyzed using multivariable regression; receipt of next scheduled HPV vaccine dose and 3-dose series completion. There were 221 parents who completed the baseline survey (11% response rate) and 164 with available follow-up data; 60% of their adolescent children received a next HPV vaccine dose and 38% completed the vaccine series at follow-up. Decrease in parents' uncertainties was a significant predictor of vaccine receipt, with each 1-point reduction in uncertainties score associated with 4.9 higher odds of receipt of the next vaccine dose. Higher baseline harms score was the only significant predictor of lower series completion. Reductions in parents' uncertainties appeared to result in greater likelihood of their children receiving the HPV vaccine. Only baseline concerns about vaccine harms were associated with lower series completion rate. Education for parents should emphasize the HPV vaccine's safety profile.


RNA-binding proteins of KHDRBS and IGF2BP families control the oncogenic activity of MLL-AF4.
Chromosomal translocation generates the MLL-AF4 fusion gene, which causes acute leukemia of multiple lineages. MLL-AF4 is a strong oncogenic driver that induces leukemia without additional mutations and is the most common cause of pediatric leukemia. However, establishment of a murine disease model via retroviral transduction has been difficult owning to a lack of understanding of its regulatory mechanisms. Here, we show that MLL-AF4 protein is post-transcriptionally regulated by RNA-binding proteins, including those of KHDRBS and IGF2BP families. MLL-AF4 translation is inhibited by ribosomal stalling, which occurs at regulatory sites containing AU-rich sequences recognized by KHDRBSs. Synonymous mutations disrupting the association of KHDRBSs result in proper translation of MLL-AF4 and leukemic transformation. Consequently, the synonymous MLL-AF4 mutant induces leukemia in vivo. Our results reveal that post-transcriptional regulation critically controls the oncogenic activity of MLL-AF4; these findings might be valuable in developing novel therapies via modulation of the activity of RNA-binding proteins.


Analysing passenger network changes: The case of Hong Kong.
Passenger throughput at Hong Kong International Airport (HKIA) has shown steady growth since its opening. Various aspects relating to HKIA have been studied in prior literature. This paper investigated changes in HKIA's passenger network for the period of 2001-2012 and used the gravity model to examine the key factors explaining its passenger traffic flows. The findings suggested that HKIA's passenger network has changed significantly and expanded to many new different destinations. Two regions (East Asia and Southeast Asia) were the most important markets for HKIA, and most key destinations connected by Hong Kong showed healthy growth. Nine factors could explain passenger traffic flows between Hong Kong and its key destinations: Hong Kong GDP per capita, GDP per capita of destinations connected by HKIA, distance, airport hub status of the destination airport, tourist destinations connected by HKIA, numbers of passenger airlines in service, bilateral trade flows, speaking a common language and having strong cultural/colonial links with Hong Kong, and the route presence of Cathay Pacific.


Changed colonic profile of P-selectin, platelet-endothelial cell adhesion molecule-1 (PECAM-1), intercellular adhesion molecule-1 (ICAM-1), ICAM-2, and ICAM-3 in inflammatory bowel disease.
Cell adhesion molecules (CAM) are essential for the capture and migration of leucocytes. Ulcerative colitis (UC) and Crohn's disease (CD) are characterized by a continuous infiltration of leucocytes into intestinal tissue, and the colonic contents of P-selectin, PECAM-1, ICAM-1, ICAM-2, and ICAM-3 were therefore studied. Concentrations of these cell adhesion molecules were measured by an ELISA technique in sonicated colonic tissue from patients with UC and CD and controls with non-inflammatory disease and compared with the diagnosis and disease activity. P-selectin, PECAM-1, and ICAM-1 concentrations were elevated in UC patients compared with controls (P = 0.034, P = 0.014, P = 0.017, respectively), whereas that of ICAM-2 was not. The concentrations of these CAM did not differ in CD. In contrast, higher concentrations of ICAM-3 were found in the CD patients than in either UC (P = 0.001) or controls (P = 0.004). The CAM concentrations increased with disease activity, although only ICAM-1 was significantly elevated (P = 0.017). As considerable differences were found between UC and CD with comparable stages of inflammation, the mere presence of inflammation cannot solely explain the results. The observed differences in the CAM concentrations in UC and CD support the hypothesis that UC and CD are two distinct disease entities with separate pathogenic mechanisms.


Structural differences in amyloid-β fibrils from brains of nondemented elderly individuals and Alzheimer's disease patients.
Although amyloid plaques composed of fibrillar amyloid-β (Aβ) assemblies are a diagnostic hallmark of Alzheimer's disease (AD), quantities of amyloid similar to those in AD patients are observed in brain tissue of some nondemented elderly individuals. The relationship between amyloid deposition and neurodegeneration in AD has, therefore, been unclear. Here, we use solid-state NMR to investigate whether molecular structures of Aβ fibrils from brain tissue of nondemented elderly individuals with high amyloid loads differ from structures of Aβ fibrils from AD tissue. Two-dimensional solid-state NMR spectra of isotopically labeled Aβ fibrils, prepared by seeded growth from frontal lobe tissue extracts, are similar in the two cases but with statistically significant differences in intensity distributions of cross-peak signals. Differences in solid-state NMR data are greater for 42-residue amyloid-β (Aβ42) fibrils than for 40-residue amyloid-β (Aβ40) fibrils. These data suggest that similar sets of fibril polymorphs develop in nondemented elderly individuals and AD patients but with different relative populations on average.


Bronchial epithelial cell transcriptome shows endotype heterogeneity of asthma in patients with NSAID-exacerbated respiratory disease.
Nonsteroidal anti-inflammatory drugs-exacerbated respiratory disease (N-ERD) is currently classified as a type-2 (T2) immune-mediated disease characterized by asthma, chronic rhinosinusitis, and hypersensitivity to cyclooxygenase-1 inhibitors. The aim of this study was to characterize immunological endotypes of N-ERD based on the gene expression profile in the bronchial epithelium. mRNA transcriptome (mRNA-sequencing) was analyzed in bronchial brushings from patients with N-ERD (n = 22), those with nonsteroidal anti-inflammatory drug-tolerant asthma (NTA, n = 21), and control subjects (n = 11). Additionally, lipid and protein mediators were measured in bronchoalveolar lavage fluid (BALF). Initial analysis of the entire asthma group revealed 2 distinct gene expression signatures: "T2-high" with increased expression of T2-related genes (eg, CLCA1, CST1), and "proinflammatory" characterized by the expression of innate immunity (eg, FOSB, EGR3) and IL-17A response genes. These endotypes showed similar prevalence in N-ERD and NTA (eg, T2-high: 33% and 32%, respectively). T2-high asthma was characterized by increased expression of mast cell and eosinophil markers, goblet cell hyperplasia, and elevated LTE4 and PGD2 in BALF. Patients with a proinflammatory endotype showed mainly neutrophilic inflammation and increased innate immunity mediators in BALF. Furthermore, the proinflammatory signature was associated with a more severe course of asthma and marked airway obstruction. These signatures could be recreated in vitro by exposure of bronchial epithelial cells to IL-13 (T2-high) and IL-17A (proinflammatory). T2-high signature was found only in one-third of patients with N-ERD, which was similar to what was found in patients with NTA. The proinflammatory endotype, which also occurred in N-ERD, suggests a novel mechanism of severe disease developing on a non-T2 background.


Erratum: Parental acceptance of the utilization of silver diamine fluoride on their child's primary and permanent teeth [Corrigendum].
[This corrects the article DOI: 10.2147/PPA.S205686.].


Breastfeeding by a mother who is a triple amputee: a case report.
Breastfeeding can be especially difficult for the physically challenged mother. This case report describes the challenges encountered by one disabled mother. A strong desire to succeed and a good support system, as well as being able to adapt to circumstances, formed the basis for success.


Bayesian Dose-Finding in Two Treatment Cycles Based on the Joint Utility of Efficacy and Toxicity.
A phase I/II clinical trial design is proposed for adaptively and dynamically optimizing each patient's dose in each of two cycles of therapy based on the joint binary efficacy and toxicity outcomes in each cycle. A dose-outcome model is assumed that includes a Bayesian hierarchical latent variable structure to induce association among the outcomes and also facilitate posterior computation. Doses are chosen in each cycle based on posteriors of a model-based objective function, similar to a reinforcement learning or Q-learning function, defined in terms of numerical utilities of the joint outcomes in each cycle. For each patient, the procedure outputs a sequence of two actions, one for each cycle, with each action being the decision to either treat the patient at a chosen dose or not to treat. The cycle 2 action depends on the individual patient's cycle 1 dose and outcomes. In addition, decisions are based on posterior inference using other patients' data, and therefore the proposed method is adaptive both within and between patients. A simulation study of the method is presented, including comparison to two-cycle extensions of the conventional 3+3 algorithm, continual reassessment method, and a Bayesian model-based design, and evaluation of robustness.


Montelukast, compared with fluticasone, for control of asthma among 6- to 14-year-old patients with mild asthma: the MOSAIC study.
Guidelines recommend daily controller therapy for mild persistent asthma. Montelukast has demonstrated consistent benefit in controlling symptoms of asthma and may be an alternative, orally administered, nonsteroidal agent for treating mild asthma. The Montelukast Study of Asthma in Children (MOSAIC study) was a 12-month, multicenter, randomized, double-blind, noninferiority trial to determine the effect of once-daily, orally administered montelukast (5 mg) (n = 495), compared with twice-daily, inhaled fluticasone (100 microg) (n = 499), on the percentage of asthma rescue-free days (RFDs) (any day without asthma rescue medication and with no asthma-related resource use). Patients 6 to 14 years of age had mild persistent asthma (average percentage of predicted forced expiratory volume in 1 second: 87.2%; RFDs at baseline: 64%). Montelukast would be considered not inferior to fluticasone if the upper limit of the 95% confidence interval for the difference in mean percentages of RFDs (fluticasone minus montelukast) was above -7% (a difference of approximately 2 days/month). The mean percentage of RFDs was 84.0% in the montelukast group and 86.7% in the fluticasone group. The least-squares mean difference was -2.8% (95% confidence interval: -4.7% to -0.9%), within the noninferiority limit of -7%. The proportion of patients requiring systemic corticosteroids and the number of patients with an asthma attack were greater in the montelukast group. Both montelukast and fluticasone were well tolerated. Montelukast was demonstrated to be not inferior to fluticasone in increasing the percentage of RFDs among 6- to 14-year-old patients with mild asthma. Secondary end points, including percentage of predicted forced expiratory volume in 1 second value, days with beta-receptor agonist use, and quality of life, improved in both groups but were significantly better in the fluticasone treatment group.


Anti-c-MET Nanobody - a new potential drug in multiple myeloma treatment.
c-MET is the tyrosine kinase receptor of the hepatocyte growth factor (HGF). HGF-c-MET signaling is involved in many human malignancies, including multiple myeloma (MM). Recently, multiple agents have been developed directed to interfere at different levels in HGF-c-MET signaling pathway. Nanobodies are therapeutic proteins based on the smallest functional fragments of heavy-chain-only antibodies. In this study, we wanted to determine the anticancer effect of a novel anti-c-MET Nanobody in MM. We examined the effects of an anti-c-MET Nanobody on thymidine incorporation, migration, adhesion of MM cells, and osteoblastogenesis in vitro. Furthermore, we investigated the effects of the Nanobody on HGF-dependent c-MET signaling by Western blotting. We show that the anti-c-MET Nanobody effectively inhibited thymidine incorporation of ANBL-6 MM cells via inhibition of an HGF autocrine growth loop and thymidine incorporation in INA-6 MM cells induced by exogenous HGF. HGF-induced migration and adhesion of INA-6 were completely and specifically blocked by the Nanobody. Furthermore, the Nanobody abolished the inhibiting effect of HGF on bone morphogenetic protein-2-induced alkaline phosphatase activity and the mineralization of human mesenchymal stem cells. Finally, we show that the Nanobody reduced phosphorylation of tyrosine residues in c-MET, MAPK, and Akt. We also compared the Nanobody with anti-c-MET monoclonal antibodies and revealed the similar or better effect. The anti-c-MET Nanobody inhibited MM cell migration, thymidine incorporation, and adhesion, and blocked the HGF-mediated inhibition of osteoblastogenesis. The anti-c-MET Nanobody might represent a novel therapeutic agent in the treatment of MM and other cancers driven by HGF-c-MET signaling.


Treatment of acute total atelectasis. Use of a double lumen tube.
Three cases are described of complete collapse of a lung in the absence of bronchial obstruction. The condition was treated by the application of a sustained high pressure (6 kPa) to the affected lung through one limb of a double lumen bronchial tube whilst intermittent positive pressure ventilation was continued through the other limb.


Problem-based learning of psychopathology in a traditional curriculum using multiple conceptual models.
A course in basic psychopathology is described in which problem-based learning is implemented in small groups in a traditional medical school curriculum. Simulated patients are utilized to provide the problem data and to allow for practice in medical interviewing. The problem-based portion of the course focuses on the explanation of various psychiatric disorders using an integration of four conceptual models: the medical/biological; the behavioural/learning; the sociocultural; and the psychodynamic. Reception of the course, based on student evaluations as well as teachers' enthusiasm and participation, has been positive for the 6 years the course has existed in this format, lending support to the conclusion that problem-based methods can be successfully integrated into a traditional lecture-based curriculum.


Hyperelastic remodeling in the intrauterine growth restricted (IUGR) carotid artery in the near-term fetus.
A constitutive model for a fiber reinforced hyperelastic material was applied to understand arterial fiber remodeling in a sheep model of Intrauterine Growth Restriction (IUGR). IUGR is associated altered hemodynamics characterized by increased resistance to blood flow in the placenta and elevated fetal arterial pressure and pulsatility. The constitutive model describes the collagen contribution to the mechanics within the arterial wall in both control and IUGR carotid artery through defining the material modulus and the orientation of the microstructure. A sheep model of placental insufficiency induced IUGR (PI-IUGR) was created by exposure of the pregnant ewe to elevated ambient temperatures. Experimental data was collected using pressure-diameter measurements to measure passive compliance in control and PI-IUGR carotid arteries. The constitutive model was optimized to fit the experimental data predicting the material parameters. Specifically, the collagen fiber predicted angle (γ) in the control artery was 49.9° from the circumferential axis while the PI-IUGR was 16.6° with a 23.5% increase in fiber orientation (κ). Quantitative assessment of collagen fiber orientation in secondary harmonic generation images confirmed the shift in orientation between the two groups. Together these suggest vascular remodeling of the ECM fiber orientation plays a major role in arterial stiffening in the PI-IUGR near-term fetal sheep.


Tyrosine hydroxylase dephosphorylation by protein phosphatase 2A in bovine adrenal chromaffin cells.
This study was undertaken to characterise the protein phosphatases in bovine adrenal chromaffin cells acting on tyrosine hydroxylase. Cells were pre-labelled with 32Pi and permeabilized with digitonin. The extent of dephosphorylation of Ser-8, Ser-19, Ser-31 and Ser-40 on tyrosine hydroxylase was found to be 30%, 38%, 37% and 71% respectively over 5 min. For Ser-19, Ser-31 and Ser-40 the dephosphorylation was entirely due to protein phosphatase 2A, as the dephosphorylation could be completely blocked by microcystin, but not by the protein phosphatase I inhibitory peptide. Permeabilization did not change the distribution of protein phosphatase 2A or tyrosine hydroxylase, or the activity of PP2A, from that occurring in intact cells. The dephosphorylation of Ser-8 was not altered by any inhibitor, suggesting the involvement of other protein phosphatases. The method developed here can be used to determine the protein phosphatases acting on substrates in conditions closely approximating those in situ, including the endogenous state of substrate phosphorylation and phosphatase location.


[Tropical and travel-related dermatomycoses : Part 2: cutaneous infections due to yeasts, moulds, and dimorphic fungi].
Besides dermatophytoses, a broad range of cutaneous infections due to yeasts and moulds may occur in subtropical and tropical countries where they can affect travellers. Not to be forgotten are endemic occurring dimorphic or biphasic fungi in countries with hot climate, which cause systemic and secondary cutaneous infections in immunosuppressed and immunocompetent people. In the tropics, the prevalence of pityriasis versicolor, caused by the lipophilic yeast Malassezia spp., is about 30-40 %, in distinct areas even 50 %. Increased hyperhidrosis under tropical conditions and simultaneously humidity congestion have to be considered as significant disposing factors for pityriasis versicolor. In tropical countries, therefore, an exacerbation of a preexisting pityriasis versicolor in travellers is not rare. Today, mostly genital yeast infections due to the new species Candida africana can be found worldwide. Due to migration from Africa this yeast pathogen has reached Germany and Europe. Eumycetomas due to mould fungi are rarely diagnosed in Europe. These deep cutaneous mould infections are only found in immigrants from African countries. The therapy of eumycetoma is protracted and often not successful. Cutaneous cryptococcoses due to the yeast species Cryptococcus neoformans and Cryptococcus gattii occur worldwide; however, they are found more frequently in the tropics. Immunosuppressed patients, especially those with HIV/AIDS, are affected by cryptococcoses. Furthermore, Cryptococcus gattii also causes infections in immunocompetent hosts in Central Africa, Australia, California, and Central America.Rarely found are infections due to dimorphic fungi after travel to countries where these fungal pathogens are endemic. In individual cases, cutaneous or lymphogenic transferred sporotrichosis due to Sporothrix schenkii can occur. Furthermore, scarcely known is secondary cutaneous coccidioidomycosis due to Coccidioides immitis after travelling to desert-like endemic regions in southwestern states of the United States and in Latin America, where primary respiratory infection due to this biphasic fungus can be acquired. The antifungal agent itraconazole is the treatment of choice for sporotrichosis and coccidioidomycosis. Talaromyces marneffei-until recently known as Penicillium marneffei-is only found in Southeastern Asia. Mycosis due to this dimorphic fungus has to be considered as an AIDS-defining opportunistic infection. After hematogeneous spread, Talaromyces marneffei affects the skin and mucous membranes of the mouth. Amphotericin B and itraconazole can be used for therapy.


Effect of sulfate on the methanogenic activity of a bacterial culture from a brewery wastewater during glucose degradation.
The maximum specific methanogenic activity (SMA) of a sludge originating from a brewery wastewater treatment plant on the degradation of glucose was investigated at various levels of sulfate on a specific loading basis. Batch experiments were conducted in serum bottles at pH 7 and 35 degrees C. A comparison of the values indicates that the SMA of this mixed culture was increased and reached its highest level of 0.128 g CH4 gas COD/(g VSS x d) when biomass was in contact with sulfate at a ratio of 1:0.114 by weight.


The structures of the asparagine-linked sugar chains of human apolipoprotein B-100.
The asparagine-linked sugar chains of human apolipoprotein B-100 were liberated from the polypeptide portion by hydrazinolysis followed by N-acetylation and NaB3H4 reduction. Their structures were elucidated by sequential exoglycosidase digestion in combination with methylation analysis after fractionation by paper electrophoresis and gel permeation chromatography. One neutral and two acidic fractions were obtained by paper electrophoresis in a molar ratio of 7:8:5. The neutral fraction contained high-mannose type oligosaccharides consisting of Man5GlcNAc2 to Man9GlcNAc2. The acidic fractions contained monosialylated and disialylated biantennary complex type oligosaccharides. As minor components in the monosialylated fraction, biantennary complex-type oligosaccharides which were absent one terminal galactose residue, monoantennary complex type, and hybrid type oligosaccharides were detected. Apolipoprotein B-100 was calculated to contain 5-6 mol of high-mannose type and 8-10 mol of complex type oligosaccharides per mole protein.


Neurovascular interactions in skin wound healing.
Skin wound healing is a complex and dynamic biological process that involves many different cell types, the extracellular matrix, and mediators, such as neuropeptides, growth factors, and cytokines. Similar to diseases of the central nervous system, neurovascular interactions have been shown to play a pivotal role in skin wound healing, for example, as seen in the delayed healing of denervated skin. In aspects involving neurovascular interactions, while angiogenesis is considered important, physiological and pathological roles of these interactions in skin wound healing remain unclear. In this review, we discuss recent findings on neurovascular interactions in skin wound healing, with a particular focus on angiogenesis.


Strict insulin therapy normalises organ nitrogen contents and the capacity of urea nitrogen synthesis in experimental diabetes in rats.
Rats with experimental diabetes due to streptozotocin (75 mg/kg body weight) and free access to food were divided into two groups. One group (n = 9) was optimally treated with insulin (glucosuria less than 4.0 mmol/24 h), using heat treated very long-acting ultralente insulin. The other group (n = 10) was poorly treated with insulin (glucosuria 20-30 mmol/24 h). The nitrogen balance and energy balance of optimally treated diabetic rats was positive and not different from the control group (n = 6). In the poorly treated diabetic rats the nitrogen balance was reduced whereas the energy balance was not different from that of control rats. After 4 weeks the fasting glucagon was: 50 +/- 21 ng/l (mean +/- SEM) in control rats, 62 +/- 18 ng/l in optimally treated diabetic rats and 249 +/- 58 ng/l in poorly treated diabetic rats (p less than 0.01). The capacity of urea nitrogen synthesis determined during alanine loading was: 9.6 +/- 1.0 mumol/(min 100 g body weight) in control rats, 10.6 +/- 1.7 mumol/(min 100 g body weight) in optimally treated diabetic rats and 17.3 +/- 1.3 mumol/(min 100 g body weight) in poorly treated diabetic rats (p less than 0.01). Nitrogen contents of carcass, heart, intestines, liver, and kidneys as determined by Kjeldahl analyses were identical in control rats and optimally treated diabetic rats.(ABSTRACT TRUNCATED AT 250 WORDS)


Acute infantile encephalopathy predominantly affecting the frontal lobes (AIEF): a novel clinical category and its tentative diagnostic criteria.
Acute infantile encephalopathy predominantly affecting the frontal lobes (AIEF) is proposed as a novel form of acute encephalopathy in infancy. To establish the diagnostic criteria for AIEF, we reviewed the clinical data of 10 patients who were seen by us and diagnosed as having AIEF, and those of 7 patients in the literature compatible with the diagnosis of AIEF. The mean age of onset was 1 year and 7 months. Boys and girls were equally affected. There is always an association with hyperpyrexia due to viral illness. Manifestations at the onset were convulsive status epilepticus and prolonged coma followed by signs of frontal lobe dysfunction such as a lack of spontaneity and regression of verbal functions. Imaging studies demonstrated edematous changes of the bilateral frontal lobes, which showed increased cerebral perfusion initially but attenuated perfusion several weeks later. The recovery of intellectual deficit was generally slower than that of motor disability. Based on these findings, we propose tentative diagnostic criteria of AIEF.


Drug resistance in cancer: a perspective.
Drug resistance remains the thorniest obstacle in developing improved systemic therapies for disseminated cancer. The combination of genetic instability together with the great molecular heterogeneity that are displayed by malignant cells makes constructing effective, rational treatment programs difficult in the extreme. However, new insights into the action of antitumor agents at the molecular level plus greater understanding of the relationship of drug resistant states to the fundamental abnormalities that generate malignancy point the way to producing therapies that are more specific and therapeutically effective. However, a non-trival problem is the drug development system itself which is currently poorly set up to yield patient specific drug programs in a timely fashion.


Clarification of the dispensability of PDX1.2 for Arabidopsis viability using CRISPR/Cas9.
PDX1.2 has recently been shown to be a regulator of vitamin B6 biosynthesis in plants and is implicated in biotic and abiotic stress resistance. PDX1.2 expression is strongly and rapidly induced by heat stress. Interestingly, PDX1.2 is restricted to eudicota, wherein it behaves as a non-catalytic pseudoenzyme and is suggested to provide an adaptive advantage to this clade. A first report on an Arabidopsis insertion mutant claims that PDX1.2 is indispensable for viability, being essential for embryogenesis. However, a later study using an independent insertion allele suggests that knockout mutants of pdx1.2 are viable. Therefore, the essentiality of PDX1.2 for Arabidopsis viability is a matter of debate. Given the important implications of PDX1.2 in stress responses, it is imperative to clarify if it is essential for plant viability. We have studied the previously reported insertion alleles of PDX1.2, one of which is claimed to be essential for embryogenesis (pdx1.2-1), whereas the other is viable (pdx1.2-2). Our study shows that pdx1.2-1 carries multiple T-DNA insertions, but the T-DNA insertion in PDX1.2 is not responsible for the loss of embryogenesis. By contrast, the pdx1.2-2 allele is an overexpressor of PDX1.2 under standard growth conditions and not a null allele as previously reported. Nonetheless, upregulation of PDX1.2 expression under heat stress is impaired in this mutant line. In wild type Arabidopsis, studies of PDX1.2-YFP fusion proteins show that the protein is enhanced under heat stress conditions. To clarify if PDX1.2 is essential for Arabidopsis viability, we generated several independent mutant lines using the CRISPR-Cas9 gene editing technology. All of these lines are viable and behave similar to wild type under standard growth conditions. Reciprocal crosses of a subset of the CRISPR lines with pdx1.2-1 recovers viability of the latter line and demonstrates that knocking out the functionality of PDX1.2 does not impair embryogenesis. Gene editing reveals that PDX1.2 is dispensable for Arabidopsis viability and resolves conflicting reports in the literature on its function.


Priming intelligent split menus with text corpora for computerized patient record data-entry.
This paper describes a methodology for using the knowledge in existing health care text corpora to prime intelligent split menus for provider data-entry. A split menu is one where the top portion of a menu list is organized by user-selection frequency and the bottom portion of the list is traditionally organized in alphabetical order. A simulation shows that data-entry with these intelligent split menus requires between two and five times less effort (in terms of user selections or mouse clicks) than menus arranged alphabetically. This paper uses a corpus from echocardiography to develop the simulation. The methodology uses statistical associations between word categories in the corpus such as 'anatomy' or 'pathology' to prime the frequency ordering of the menus. A dictionary of terms contains the categorical information. After the initial priming, actual user selections are used to update the frequencies used to adapt to providers' individual data-entry patterns.


Use of a structured medication history to establish medication use at admission to an old age psychiatric clinic: a prospective observational study.
Medication reconciliation results in fewer adverse drug events. The first step in medication reconciliation is to carry out a structured interview about medication use. It is not known whether such an interview is useful in inpatient old age psychiatry. The object of this study was to determine at admission the number of discrepancies in medication use, comparing the structured history of medication use (SHIM) procedure with the usual procedure for taking the medication history. A prospective observational study was conducted. All consecutive patients aged 55 years and older admitted from January until April 2011 to the inpatient old age psychiatric clinic of a large psychiatric teaching hospital in The Hague, the Netherlands, were eligible for inclusion; 50 patients were included. In every patient, the usual procedure (medication history-taking at admission by the treating physician) was compared with the SHIM procedure administered by the researcher. The SHIM procedure consists of a structured interview with the patient about the actual use of medication, incorporating the information from the community pharmacy and the patient's medications brought to the interview. The main outcome was the number of discrepancies in recorded medication use between the SHIM and the usual procedure. In total, 100 discrepancies (median 2 per patient, range 0-8) in medication use were identified; 78 % (n = 39) of the patients had at least one discrepancy. Of the discrepancies, 69 % were drug omissions, and 31 % were drug additions or discrepancies in the frequency or dosage of medications. Eighty-two percent of all discrepancies were potentially clinically relevant. In 24 % of the patients, the discrepancies had clinical consequences. The number of discrepancies that were found suggests that the usual procedure for taking the medication history can be improved. The SHIM procedure enables a comprehensive and accurate overview of the medication used by older patients admitted to a psychiatric hospital, and contributes to the prevention of clinically relevant adverse drug events.


Studies on the uptake and metabolism of dibenz(b,f)-1,4-oxazepine (CR) by guinea-pig cornea.
The uptake and metabolic fate of the sensory irritant dibenz(b,f)-1,4-oxazepine (CR) have been investigated in intact cornea and corneal homogenates using 3H-labelled CR. The cornea metabolises CR to its lactam derivative (10,11-dihydro-10-oxo-dibenz(b,f)-1,4-oxazepine) by a process which appears to be located in the cell cytoplasm and which is easily saturated. Uptake studies with higher concentrations of [3H]CR (1 X10(-5) M) which saturate lactam biosynthesis, suggest that CR may bind, with low affinity, to sites within the corneal cells. The possible roles of CR metabolism and CR binding in chemical sensory irritation are discussed.


Integrative molecular roadmap for direct conversion of fibroblasts into myocytes and myogenic progenitor cells.
Transient MyoD overexpression in concert with small molecule treatment reprograms mouse fibroblasts into induced myogenic progenitor cells (iMPCs). However, the molecular landscape and mechanisms orchestrating this cellular conversion remain unknown. Here, we undertook an integrative multiomics approach to delineate the process of iMPC reprogramming in comparison to myogenic transdifferentiation mediated solely by MyoD. Using transcriptomics, proteomics, and genome-wide chromatin accessibility assays, we unravel distinct molecular trajectories that govern the two processes. Notably, only iMPC reprogramming is characterized by gradual up-regulation of muscle stem cell markers, unique signaling pathways, and chromatin remodelers in conjunction with exclusive chromatin opening in core myogenic promoters. In addition, we determine that the Notch pathway is indispensable for iMPC formation and self-renewal and further use the Notch ligand Dll1 to homogeneously propagate iMPCs. Collectively, this study charts divergent molecular blueprints for myogenic transdifferentiation or reprogramming and underpins the heightened capacity of iMPCs for capturing myogenesis ex vivo.


Antioxidant and anticataractogenic effects of topical captopril in diquat-induced cataract in rabbits.
1-[(2s)-3-Mercapto-2-methylpropionyl]-L-proline (captopril), an antihypertensive and free radical scavenger, protected the rabbit lens from peroxidative and oxidative damage induced by 1 mM diquat in vitro. To evaluate the anticataract efficacy of captopril, an experimental group of five rabbits was treated with topical captopril (1% in 0.15 M NaCl, w/v), and 50 microliters was instilled onto both eyes four times a day for a total of 8 weeks. Following the same procedure, the eyes of five rabbits were treated with topical 0.15 M NaCl as a control for captopril treatment. At the end of the first week of treatment, a single intravitreal dose of 120 nmole diquat in 30 microliters of 0.15 M NaCl was injected into the right eye of each rabbit of both the groups. As a control for intravitreal diquat injection, the left eye of all the rabbits were injected with the diluent, 30 microliters per eye. The intravitreal diquat or its diluent injection was only for one time. From slit-lamp biomicroscopic observation of the diquat-injected right eyes, the anticataract effect of captopril in the treatment group was indicated by the finding that in four of five rabbits the cataract did not advance; whereas in four of five rabbits treated with the diluent the cataract progressed to grade 3. The lenses in the diluent-injected control left eyes of the rabbits treated with the captopril or diluent were normal. However, since the number of animals used for the in vivo studies was few, further confirmation of the anticataract effect of captopril is necessary. In diquat-injected right eyes of animals treated with captopril, the integrated rate of O2- production was about 50% less (p less than .001) in the aqueous humor, vitreous humor, and lens, compared with O2-, 33.49 +/- 2.26 microM (mean +/- SEM) in the aqueous humor, 17.12 +/- 0.75 microM in the vitreous humor, and 31.44 +/- 1.29 nmole/g wet weight in the lens of the diquat-injected right eyes treated with the diluent. Similar significant (p less than .01) differences in the production of .OH and H2O2 in eye tissues were also observed.(ABSTRACT TRUNCATED AT 400 WORDS)


Covid-19 vaccine hesitancy, conspiracist beliefs, paranoid ideation and perceived ethnic discrimination in a sample of University students in Venezuela.
Due to complex social, political and economic causes, Venezuela has encountered difficulties managing the Covid-19 pandemic. Although a vaccination program has started, it is still comparatively slow and largely inefficient. One particular challenge has been vaccine hesitancy. Venezuelan policymakers have traditionally not rendered much attention to ethnic disparities. In this study, we assess whether vaccine hesitancy varies across ethnic groups, in a sample of 273 Venezuelan university students. Results come out showing that marginalized ethnic groups in Venezuela are more prone to vaccine hesitancy, and also have greater levels of acceptance regarding conspiracy theories. Coefficients of correlation of ethnic discrimination with vaccine hesitancy and conspiracy beliefs are moderate. Coefficients of correlation of paranoid ideation with vaccine hesitancy and conspiracy beliefs are weak. This suggests that in order to successfully complete the vaccination program, policymakers in Venezuela must begin to approach racial disparities.


Intermittent fasting, adipokines, insulin sensitivity, and hypothalamic neuropeptides in a dietary overload with high-fat or high-fructose diet in mice.
The intermittent fasting (IF) might have benefits on metabolism and food intake. Twelve-week old C57BL/6 J mice were fed a control diet (C, 10% kcal fat), a high-fat diet (HF, 50% kcal fat) or a high-fructose diet (HFru, 50% kcal fructose) for 8 weeks, then half of the animals in each group underwent IF (24 h fed, 24 h fasting) for an additional 4 weeks. Although food intake on the fed day remained the same for all groups, all fasting groups showed a reduction in body mass compared to their counterparts. IF reduced total cholesterol, triacylglycerol, fasting glucose, fasting insulin resistance index, and plasma leptin, but increased plasma adiponectin. IF reduced Leptin gene expression in the HF-IF group, but increased proinflammatory markers in the hypothalamus, also in the C-IF group. Both groups HFru-IF and C-IF, showed alterations in the leptin signaling pathway (Leptin, OBRb, and SOCS3), mainly in the HFru-IF group, suggesting leptin resistance. NPY and POMC neuropeptides labeled the neurons of the hypothalamus by immunofluorescence, corroborating qualitatively other quantitative findings of the study. In conclusion, current results are convincing in demonstrating the IF effect on central regulation of food intake control, as shown by NPY and POMC neuropeptide expressions, resulting in a lower weight gain. Besides, IF improves glycemia, lipid metabolism, and consequently insulin and leptin resistance. However, there is increased expression of inflammatory markers in mouse hypothalamus challenged by the HF and HFru diets, which in the long term may induce adverse effects.


Mid-term results of transphyseal anterior cruciate ligament reconstruction in children and adolescents.
Optimal therapy for anterior cruciate ligament (ACL) rupture in the paediatric population still provokes controversy. Although conservative and operative treatments are both applied, operative therapy is slightly favored. Among available surgical techniques are physeal-sparing reconstruction and transphyseal graft fixation. The aim of this study was to present our mid-term results after transphyseal ACL reconstruction. Fifteen young patients (mean age=12.8±2.6, range=6.2-15.8 years, Tanner stage=2-4) with open physis and traumatic anterior cruciate rupture who had undergone transphyseal ACL reconstruction with unilateral quadriceps tendon graft were prospectively analyzed. All children were submitted to radiological evaluation to determine the presence of clearly open growth plates in both the distal femur and proximal tibia. Postoperatively, all patients were treated according to a standardized rehabilitation protocol and evaluated by radiographic analysis and the Lysholm-Gillquist and IKDC 2000 scores. Their health-related quality of life was measured using the SF-12 PCS (physical component summary) and MCS (mental component summary) questionnaires. Mean postoperative follow-up was 4.1 years. Mean Lysholm-Gillquist score was 94.0. Thirteen of the 15 knees were considered nearly normal on the IKDC 2000 score. The mean SF-12 questionnaire score was 54.0±4.8 for SF-12 PCS and 59.1±3.7 for SF-12 MCS. No reruptures were observed. Radiological analysis detected one knee with valgus deformity. All patients had a normal gait pattern without restrictions. Transphyseal reconstruction of the anterior cruciate ligament shows satisfactory mid-term results in the immature patient.


Single-Cell RNA Analysis Reveals Cell-Intrinsic Functions of CAR T Cells Correlating with Response in a Phase II Study of Lymphoma Patients.
Although CD19 chimeric antigen receptor T cells (CAR-T) therapy has shown remarkable success in B-cell malignancies, a substantial fraction of patients do not obtain a long-term clinical response. This could be influenced by the quality of the individual CAR-T infusion product. To shed some light on this, clinical outcome was correlated to characteristics of CAR-T infusion products. In this phase II study, patients with B-cell lymphoma (n = 23) or leukemia (n = 1) received one or two infusions of third-generation CD19-directed CAR-Ts (2 × 108/m2). The clinical trial was registered at clinicaltrials.gov: NCT03068416. We investigated the transcriptional profile of individual CD19 CAR-T infusion products using targeted single-cell RNA sequencing and multicolor flow cytometry. Two CAR-T infusions were not better than one in the settings used in this study. As for the CAR-T infusion products, we found that effector-like CD8+CAR-Ts with a high polyfunctionality, high cytotoxic and cytokine production profile, and low dysfunctional signature were associated with clinical response. An extended ex vivo expansion time during CAR-T manufacturing negatively influenced the proportion of effector CD8+CAR-Ts in the infusion product. We identified cell-intrinsic characteristics of effector CD8+CAR-Ts correlating with response that could be used as an indicator for clinical outcome. The results in the study also serve as a guide to CAR-T manufacturing practices.


Studies on lysophosphatidic acid action during in vitro preimplantation embryo development.
Assisted reproductive technologies, including in vitro embryo production (IVP), have been successfully used in animal reproduction to optimize breeding strategies for improved production and health in animal husbandry. Despite the progress in IVP techniques over the years, further improvements in in vitro embryo culture systems are required for the enhancement of oocyte and embryo developmental competence. One of the most important issues associated with IVP procedures is the optimization of the in vitro culture of oocytes and embryos. Studies in different species of animals and in humans have identified important roles for receptor-mediated lysophosphatidic acid (LPA) signaling in multiple aspects of human and animal reproductive tract function. The data on LPA signaling in the ovary and uterus suggest that LPA can directly contribute to embryo-maternal interactions via its influence on early embryo development beginning from the influence of the ovarian environment on the oocyte to the influence of the uterine environment on the preimplantation embryo. This review discusses the current status of LPA as a potential supplement in oocyte maturation, fertilization, and embryo culture media and current views on the potential involvement of the LPA signaling pathway in early embryo development.


Misdiagnosis in mucopolysaccharidoses.
Mucopolysaccharidosis (MPS) is a group of 13 hereditary metabolic diseases identified in humans (or 14 diseases if considering one MPS type described to date only in mice) in which an enzymatic defect results in the accumulation of glycosaminoglycans (GAG) in the lysosomes of cells. First of all, as a result of GAG storage, the proper functioning of the lysosome is disturbed; then, the cells, and finally, tissue, organs, and the whole organism malfunctions are observed. Due to the rarity, heterogeneity, and multi-systemic and progressive nature of MPS, they present a major diagnostic challenge. Due to the wide variation in symptoms and their similarity to other diseases, MPS is often misdiagnosed, usually as neurological diseases (like autism spectrum disorders, psychomotor hyperactivity, and intellectual disability) or rheumatology and orthopedic disorders (like juvenile idiopathic arthritis, Perthes disease, rickets, and muscular dystrophy). In this review article, we present the problems associated with the possibility of misdiagnosing MPS, discuss what diseases they can be confused with, and suggest ways to reduce these problems in the future.


Non-invasive continuous blood pressure prediction based on ECG and PPG fusion map.
To achieve real-time blood pressure monitoring, a novel non-invasive method is proposed in this article. Electrocardiographic (ECG) and pulse wave signals (PPG) are fused from a multi-omics signal-level perspective. A physiological signal fusion matrix and fusion map, which can estimate the blood pressure of blood loss(BPBL), are constructed. The results demonstrate the efficacy of the fusion map model, with correlation values of 0.988 and 0.991 between the estimated BPBL and the true systolic blood pressure (SBP) and diastolic blood pressure (DBP), respectively. The root mean square errors for SBP and DBP were 3.21 mmHg and 3.00 mmHg, respectively. The model validation showed that the fusion map method is capable of simultaneous highlighting of the respective characteristics of ECG and PPG and their correlation, improving the utilization of the information and the accuracy of BPBL. This article validates that physiological signal fusion map can effectively improve the accuracy of BPBL estimation and provides a new perspective for the field of physiological information fusion.


Hemorrhagic rectal ulcer caused by a deformity of the coccyx complicated by normal delivery.
A 25-year-old woman delivered her first-born child weighing 3400 g by full-term normal delivery. Bloody stool developed 3 days after delivery. Colonoscopic examination revealed two linear ulcers parallel to the anal column on the posterior side of the rectal ampulla about 5 cm from the anal ring. Coagulated blood was detected at the ulcer bottom, suggesting the site of hemorrhage. Bowel rest in the absence of oral intake resulted in the disappearance of bloody stool. Three days later colonoscopic examination revealed improvement in the ulcer. There was no sign of constipation. A lateral pelvic radiograph showed that the apex of the coccyx was flexed anteriorly. The parturient canal may have physically pressed the rectum against the apex of the coccyx during delivery, causing mucosal injury. Only a few studies have reported the complication of a rectal ulcer due to injury during delivery. Furthermore, none of the previous studies has reported a rectal ulcer caused by deformity of the coccyx.


Factors influencing the estimates of correlation between motor unit activities in humans.
Alpha motoneurons receive common synaptic inputs from spinal and supraspinal pathways. As a result, a certain degree of correlation can be observed between motoneuron spike trains during voluntary contractions. This has been studied by using correlation measures in the time and frequency domains. These measures are interpreted as reflecting different types of connectivity in the spinal networks, although the relation between the degree of correlation of the output motoneuron spike trains and of their synaptic inputs is unclear. In this study, we analyze theoretically this relation and we complete this analysis by simulations and experimental data on the abductor digiti minimi muscle. The results demonstrate that correlation measures between motoneuron output spike trains are inherently influenced by the discharge rate and that this influence cannot be compensated by normalization. Because of the influence of discharge rate, frequency domain measures of correlation (coherence) do not identify the full frequency content of the common input signal when computed from pairs of motoneurons. Rather, an increase in sampling rate is needed by using cumulative spike trains of several motoneurons. Moreover, the application of averaging filters to the spike trains influences the magnitude of the estimated correlation levels calculated in the time, but not in the frequency domain (coherence). It is concluded that the analysis of coherence in different frequency bands between cumulative spike trains of a sufficient number of motoneurons provides information on the spectrum of the common synaptic input. Nonetheless, the absolute values of coherent peaks cannot be compared across conditions with different cumulative discharge rates.


Antibody formation in laboratory animals after parenteral application of A/swine influenza virus.
Antigenicity of swine influenza viruses, Ann Arbor/31 and recombinant X-53, was compared on the different animal species. The serological investigations of animals infected with live or immunized with the inactivated virus, demonstrated a close antigenic relationship between the H and N antigens of both viruses. For inactivated vaccine preparation it was recommended, on the basis of our results, to use Ann Arbor virus instead of virus X-53.


Does obstructive sleep apnoea modulate cardiac autonomic function in paroxysmal atrial fibrillation?
The autonomic nervous system may mediate acute apnoea-induced atrial fibrillation (AF). We compared cardiac autonomic function in paroxysmal atrial fibrillation (PAF) patients with and without obstructive sleep apnoea (OSA). Case control study of 101 patients with PAF recruited at two tertiary centres. All patients underwent in-laboratory polysomnography. ECG signal demonstrating "steady state" sinus rhythm (i.e. with arrhythmic beats and respiratory events excluded) was included in the analysis. Cardiac autonomic function was assessed via measures of heart rate variability (HRV) and reported by sleep stage (REM vs Non-REM) for patients with and without OSA. Sixty-five (66.3%) of patients were male, mean age 61.5 ± 11.6 years, mean BMI 27.1 ± 4.3 kg/m2. Global measures of HRV (triangular index, total power) did not differ between PAF patients with and without OSA in either REM or non-REM sleep. Frequency-domain analysis during non-REM sleep in PAF patients with OSA showed increased cardiac parasympathetic modulation (HF-nu: 39.1 ± 15.7 vs 48.0 ± 14.6, p = 0.008) and reduced cardiac sympathetic modulation (LF-nu 54.1 ± 19.7 vs 43.7 ± 18.0, p = 0.012, LF/HF ratio: 2.1 ± 2.0 vs 1.2 ± 1.0, p = 0.007). Results remained significant after adjusting for age, sex, and BMI (adjusted p values 0.024, 0.045 and 0.018 respectively). There were no differences in HRV parameters during REM sleep. This is the first study of HRV in PAF patients with and without OSA. Our results indicate limited differences in HRV between groups. However, this work suggests a chronic increase in parasympathetic nervous modulation and relative reduction in sympathetic modulation in PAF patients with OSA during steady-state non-REM sleep.


Histocompatibility typing and the counseling of families with ankylosing spondylitis.
White individuals who are HLA B27-positive have an increased risk of developing ankylosing spondylitis or related diseases. HLA typing can be used in counseling relatives of persons with spondylitis, if the limitations of presently available data are recognized.


Studies on cell transformation.
Seven different transformation stigmata of the transformed CHO cell line, including morphological characteristics, growth behavior, cell membrane biochemical properties, and failure of fibronectin deposition, are reversed by addition of cAMP derivatives to the medium. Simultaneously the microtubular pattern changes from a sparse, relatively random set to an orderly arrangement of tubules largely parallel to each other and to the long axis of the resulting fibroblastic cell. Agents like colcemid and cytochalasin B, respectively disorganizing microtubular and particular microfilamentous structures, prevent at least certain aspects of the reverse transformation reaction induced by cAMP in interphase cells. It is proposed that malignant transformation can be effected by damage to the microtubular and microfilamentous structures which changes cell constitution and behavior in two ways: (1) chromosomal instability is introduced which promotes continuous selection for variants better able to resist environmental signals to limit reproduction and (2) a variety of metabolic defects in biochemical processes such as specific membrane functions are introduced which may alter the growth responses of the cell. This picture offers a reasonable explanation for a number of aspects of normal and malignant cell behavior.


Nerve fibre regeneration across the PNS-CNS interface at the root-spinal cord junction.
Root-spinal cord regeneration was investigated in immature and adult rats. The elongation in the dorsal root of regrowing dorsal root axons, rerouted ventral root nerve fibres (cholinergic neurons) or hypogastric nerve fibres (catecholaminergic neurons) is impeded as they meet the astrocyte dominated CNS tissue of the root. The establishment of synaptoid nerve terminals as the regrowing axons encounter astrocytes indicates a mechanism for growth inhibition other than a physical impediment in the CNS environment. The glial cells of the CNS segment in the root are influenced by the type of regenerating nerve fibres in terms of maintenance, multiplication and phenotypic expression. After a dorsal root lesion in the neonatal rat several root axons may reinnervate the spinal cord. In these rats, the normal establishment of a CNS root segment has been disrupted and the PNS-CNS border is situated central to the root-spinal cord junction. Implantation of cut dorsal roots into the spinal cord of adult rats results in the extension of processes from intrinsic spinal cord neurons out into the root. After implantation of avulsed ventral roots into the ventro-lateral aspect of the cord, axonal regrowth and functional restitution of alpha-motoneurons could be demonstrated by intracellular recordings and injections with horseradish peroxidase. These results show that regeneration can occur across a PNS-CNS interface that has been established secondary to a trauma in the mature animal and in the immature animal before the astrocyte-rich CNS root segment has been developed.


Radial Artery Access Complications: Prevention, Diagnosis and Management.
The transradial approach for cardiac catheterization, coronary angiography, and percutaneous intervention is associated with a lower risk of access site-related complications compared to the transfemoral approach. However, with increasing utilization of transradial access for not only coronary procedures but also peripheral vascular procedures, healthcare personnel are more likely to encounter radial access site complications, which can be associated with morbidity and mortality. There is significant heterogeneity in the reporting of incidence, manifestations, and management of radial access site complications, at least partly due to vague presentation and under-diagnosis. Therefore, physicians performing procedures via transradial access should be aware of possible complications and remain vigilant to prevent their occurrence. Intraprocedural complications of transradial access procedures, which include spasm, catheter kinking, and arterial dissection or perforation, may lead to patient discomfort, increased procedure time, and a higher rate of access site cross over. Post-procedural complications such as radial artery occlusion, hematoma, pseudoaneurysm, arteriovenous fistula, or nerve injury could lead to patient discomfort and limb dysfunction. When radial access site complications occur, comprehensive evaluation and prompt treatment is necessary to reduce long-term consequences. In this report, we review the incidence, clinical factors, and management strategies for radial access site complications associated with cardiac catheterization.


Bradykinin and Galectin-3 in Survived and Deceased Patients with COVID-19 Pneumonia: An Increasingly Promising Biochemical Target.
There are still no definite curative or preventive strategies for COVID-19 disease. It is crucial to fully comprehend the pathogenesis of COVID-19 infection so that we can develop expedient pharmacological protocols. While the impact of cytokine storm on COVID-19 severity has been one of the most tested hypotheses, the role of bradykinin and various other oxidative stress markers has been relatively under-researched. Their levels can be determined immediately after a hospital admission so they could be used as early predictors of the further development of the disease. The study aims at evaluating the possibility of using bradykinin and galectin-3 levels as early predictors that COVID-19 disease will progress into a severe case. Material and methods. The study was conducted as a prospective cross-sectional study. It included 47 consecutive adult patients with confirmed SARS-CoV-2 infection and COVID-19 pneumonia. All study subjects were admitted for a hospital treatment to the tertiary Clinical Hospital Center Bezanijska kosa, Belgrade, Serbia on June 2021. The blood samples were collected at the patients' admission. The analyses of demographic, radiological, and clinical data were later conducted for both groups (the deceased patients and those who survived). In addition, we analyzed the potential relations between the outcome and the levels of bradykinin and galectin-3 measured immediately after the patients were admitted to the hospital. The patients who passed away were predominantly older men with comorbidities. We recorded higher CT scores in the deceased patients and the significantly higher levels of urea, creatinine, CK, troponine, CRP, and other laboratory markers. They stayed at the ICU unit longer and required mechanical ventilation more frequently than the patients who survived. On the other hand, no differences were recorded in the time periods passing from the onset of the systems to the hospital admissions. Finally, we can highlight several independent predictors of mortality in patients with COVID-19 pneumonia, including the following: (1) patients who are 50 or more years old, (2) with in-hospital stays are longer that 4 days, (3) bradykinin levels surpass 220000 pg/ml, (4) D-dimer, creatinine, and CRP are elevated, and (5) comorbidities were present (such as hypertension and diabetes). The present study strongly supports the bradykinin storm hypothesis. Since elevated bradykinin levels have been found in most COVID-19 cases with fatal outcomes, the future therapeutical strategies for COVID-19 have to be focused on reducing bradykinin serum concentrations.


Upper limb impairments and their impact on activity measures in children with unilateral cerebral palsy.
Insights in upper limb impairments and their relationship with activity measures in children with unilateral cerebral palsy (CP) are important to optimize treatment interventions. (1) To investigate upper limb impairments and activity limitations in children with unilateral CP; (2) to compare these according to the Manual Ability Classification System (MACS), timing of lesion (congenital/acquired) and age; (3) to determine the impact of impairments on activity measures. Eighty-one children with unilateral CP aged 5-15 years (mean 9 years 11 months; congenital N=69, acquired N=12) were recruited. Body function measurements included passive range of motion (PROM), muscle tone, strength and sensibility. At activity level, the Melbourne Assessment, Assisting Hand Assessment (AHA) and Abilhand-Kids were assessed. Most PROM limitations were found for elbow extension and supination. Increased tone and weakness were most prominent in distal muscles. Stereognosis and two-point discrimination were mostly affected. Children with a lower MACS level or acquired lesion had significantly more impairments and activity limitations. In children with congenital lesions, best predictors for unimanual capacity (Melbourne Assessment) were wrist strength, stereognosis and proprioception, and for bimanual performance (AHA) wrist strength and grip strength, explaining 76% of the variance. For the Abilhand-Kids, wrist strength and stereognosis predicted 46% of the variance. Classification according to MACS and timing of lesion is important to differentiate within the wide range of impairments and activity limitations. In children with congenital lesions, unimanual capacity and bimanual performance are highly determined by distal strength, supporting the additional use of impairment-based interventions.


Danazol: an antigonadotrophic agent in the treatment of recurrent pelvic and intestinal endometriosis.
Six cases of pelvic endometriosis were treated with Danazol 400 mg daily for six months. In four of these cases, intestinal endometriosis of varying severity was also present. The initial results were very satisfactory except in one case with adenomyosis and continuous spotting. Follow-up after cessation of treatment suggests that in some cases a further period of treatment will be necessary.


Rocket UV flash spectra from the solar eclipse of March 7, 1970.
Flash spectra of the total solar eclipse throughout all its phases have been obtained in the extreme ultraviolet for the first time.


Impact of fluorination on proteolytic stability of peptides in human blood plasma.
Several factors reduce the efficacy of natural peptides as drug candidates; chief among these is their rapid digestion by human proteases. Over the last few decades, a number of strategies have been employed to increase the enzymatic stability of peptides, including the introduction of non-natural amino acids. This study aims at the investigation of the effect of side chain fluorination on the stability of peptides in human blood plasma. Ten model peptides with different non-natural amino acids were designed, synthesized and subjected to enzymatic degradation in human blood plasma. The stability of the studied peptides was followed by HPLC analysis and compared to the control peptide built with only proteinogenic residues. Four main hydrolysis products were detected and identified by mass spectrometry, three of them being characteristic cleavage products of the serine protease Elastase. A final enzymatic study with isolated Elastase validated then the outcome of the plasma study. This case study contributes to the application of fluorinated amino acids in the design of proteolytically stable peptides and proteins with potential clinical relevance.


Simulation study of PET detector configuration with thick light guide and GAPD array having large-area microcells for high effective quantum efficiency.
Light sharing PET detector configuration coupled with thick light guide and Geiger-mode avalanche photodiode (GAPD) with large-area microcells was proposed to overcome the energy non-linearity problem and to obtain high light collection efficiency (LCE). A Monte-Carlo simulation was conducted for the three types of LSO block, 4 × 4 array of 3 × 3 × 20 mm(3) discrete crystals, 6 × 6 array of 2 × 2 × 20 mm(3) discrete crystals, and 12 × 12 array of 1 × 1 × 20 mm(3) discrete crystals, to investigate the scintillation light distribution after conversion of the γ-rays in LSO. The incident photons were read out by three types of 4 × 4 array photosensors, which were PSPMT of 25% quantum efficiency (QE), GAPD1 with 50 × 50 µm(2) microcells of 30% photon detection efficiency (PDE) and GAPD2 with 100 × 100 µm(2) of 45% PDE. The number of counted photons in each photosensor was analytically calculated. The LCE, linearity and flood histogram were examined for each PET detector module having 99 different configurations as a function of light guide thickness ranging from 0 to 10 mm. The performance of PET detector modules based on GAPDs was considerably improved by using the thick light guide. The LCE was increased from 24 to 30% and from 14 to 41%, and the linearity was also improved from 0.97 to 0.99 and from 0.75 to 0.99, for GAPD1 and GAPD2, respectively. As expected, the performance of PSPMT based detector did not change. The flood histogram of 12 × 12 array PET detector modules using 3 mm light guide coupled with GAPDs was obtained by simulation, and all crystals of 1 × 1 × 20 mm(3) size were clearly identified. PET detector module coupled with thick light guide and GAPD array with large-area microcells was proposed to obtain high QE and high spatial resolution, and its feasibility was verified. This study demonstrated that the overall PET performance of the proposed design was considerably improved, and this approach will provide opportunities to develop GAPD based PET detector with a high LCE.


Effect of the rob(1;29) translocation on the fertility of beef cattle reared under extensive conditions: A 30-year retrospective study.
The Robertsonian translocation 1/29 (rob(1;29)) is the most worldwide widespread chromosomal abnormality in domestic animals. Previous studies have demonstrated its negative effect on fertility in dairy herds, but not in beef cattle extensively bred. In this study, we analysed the effect of rob(1;29) in a Retinta cattle breed data set gathered during the last 30 years. The data presented herein include rob(1;29) analysis of 11,505 cows from 251 herds, pedigree information of 24,790 animals and 67,457 calving records. Fertility was evaluated using estimated breeding values for the reproductive efficiency (Re), calculated as the percentage ratio between the number of calvings of an individual and the number expected in an optimal situation. Our results showed that cows carrying the heterozygote genotype showed a significant decrease in their Re (-5.10%, p < .001). No decrease was detected in free rob(1;29) animals and homozygous carriers. In addition, the incidence of rob(1;29) in the breed fertility was decreased to very low values after 30 years of avoiding selection of bulls' carrier as stallions. The effect of rob(1;29) on cattle fertility is only significant when the prevalence of carrier individuals is high. Selecting against the disease only by the paternal side reduced the incidence to negligible values.


Salient Measures of Hospitalist Workload.
The ideal hospitalist workload and optimal way to measure it are not well understood. To obtain expert consensus on the salient measures of hospitalist workload. This qualitative study used a 3-round Delphi technique between April 5 and July 13, 2022, involving national experts within and external to the field. Experts included hospitalist clinicians, leaders, and administrators, as well as researchers with expertise in human factors engineering and cognitive load theory. Three rounds of surveys were conducted, during which participants provided input on the salient measures of hospitalist workload across various domains. In the first round, free-text data collected from the surveys were analyzed using a directed qualitative content approach. In the second and third rounds, participants rated each measure's relevance on a Likert scale, and consensus was evaluated using the IQR. Percentage agreement was also calculated. Seventeen individuals from 14 organizations, encompassing clinicians, leaders, administrators, and researchers, participated in 3 rounds of surveys. In round 1, participants provided 135 unique qualitative comments across 10 domains, with 192 unique measures identified. Of the 192 measures presented in the second round, 6 (3%) were considered highly relevant, and 25 (13%) were considered moderately relevant. In round 3, 161 measures not meeting consensus were evaluated, with 25 (16%) considered highly relevant and 95 (59%) considered moderately relevant. Examples of measures considered highly relevant included a patient complexity score and outcome measures such as savings from hospital days avoided and clinician turnover. In this qualitative study measuring hospitalist workload, multiple measures, including those quantifying work demands and the association of those demands with outcomes, were considered relevant for measuring and understanding workloads. The findings suggest that relying on traditional measures, such as productivity-related measures and financial measures, may offer an incomplete understanding of workloads and their association with key outcomes. By embracing a broader range of measures, organizations may be able to better capture the complexity and nuances of hospitalist work demands and their outcomes on clinicians, patients, and organizations.


Cellular, Molecular and Non-Pharmacological Therapeutic Advances for the Treatment of Parkinson's Disease: Separating Hope from Hype.
Parkinson's Disease (PD) is a frustrating condition characterized by motor and nonmotor deficits majorly caused by the loss of dopaminergic cells in the Substantia Nigra pars compacta (SNc) and destruction of the nigrostriatal pathway. Despite the very respectable advances in cutting-edge approaches for the treatment of PD, there exist numerous challenges that have incapacitated the definitive treatment of this disease. This review emphasized the development of various non-pharmaceutical therapeutic approaches and mainly highlighted the cutting-edge treatments for PD including gene- and stem cell-based therapies, targeted delivery of neurotrophic factors, and brain stimulation techniques such as Transcranial Magnetic Stimulation (TMS), transcranial Direct Current Stimulation (tDCS), and Deep Brain Stimulation (DBS). The review covered various gene therapy strategies including Adeno-Associated Virus-Glutamic Acid Decarboxylase (AAV-GAD), AAV-Aromatic L-Amino Acid Decarboxylase (AAV-AADC), Lenti-AADC/Tyrosine Hydroxylase/Guanosine Triphosphate- Cyclohydrolase I (Lenti-AADC/TH/GTP-CH1), AAV-Neurturin (AAV-NRTN), α-Synuclein silencing, and PRKN gene delivery. Also, the advantages, disadvantages, and the results of trials of these methods were discussed. Finally, reasons for the failure of PD treatment were described, with the hopes separated from hypes.


Evaluating a scale of excessive mind wandering among males and females with and without attention-deficit/hyperactivity disorder from a population sample.
Recent studies highlight the role of excessive mind wandering in attention-deficit/hyperactivity disorder (ADHD) and its association with impairment. We believe assessing mind wandering could be especially relevant to individuals, including many females, who present with less externalising manifestations of ADHD. Using a new measure based on ADHD patient reports, the Mind Excessively Wandering Scale (MEWS), we previously found adults with ADHD had elevated levels of mind wandering that contributed to impairment independently of core ADHD symptoms. Using data from an online general population survey, the current study assessed the factor-structure, reliability, validity and measurement invariance of the MEWS. We also investigated sex differences in mind wandering, as well as ADHD symptoms, impairment and wellbeing in those with and without ADHD. The MEWS had a unidimensional structure, was invariant across sex, age and ADHD status, and accounted for unique variance in impairment and wellbeing beyond core ADHD symptoms. Among those with ADHD, we found no evidence for sex differences in mind wandering and among those without ADHD males had higher scores. We also found similar levels of hyperactivity/impulsivity, emotional lability, and impairment in males and females with ADHD, but males reported greater inattention and lower wellbeing. Results suggest the MEWS is a reliable and valid instrument measuring the same construct across sex, age and ADHD status, which could aid diagnosis and monitoring of outcomes.


Radon emanation from low-grade uranium ore.
Estimation of radon emanation in uranium mines is given top priority to minimize the risk of inhalation exposure due to short-lived radon progeny. This paper describes the radon emanation studies conducted in the laboratory as well as inside an operating underground uranium mine at Jaduguda, India. Some of the important parameters, such as grade/(226)Ra activity, moisture content, bulk density, porosity and emanation fraction of ore, governing the migration of radon through the ore were determined. Emanation from the ore samples in terms of emanation rate and emanation fraction was measured in the laboratory under airtight condition in glass jar. The in situ radon emanation rate inside the mine was measured from drill holes made in the ore body. The in situ(222)Rn emanation rate from the mine walls varied in the range of 0.22-51.84 × 10(-3) Bq m(-2) s(-1) with the geometric mean of 8.68 × 10(-3) Bq m(-2) s(-1). A significant positive linear correlation (r = 0.99, p < 0.001) between in situ(222)Rn emanation rate and the ore grade was observed. The emanation fraction of the ore samples, which varied in the range of 0.004-0.089 with mean value of 0.025 ± 0.02, showed poor correlation with ore grade and porosity. Empirical relationships between radon emanation rate and the ore grade/(226)Ra were also established for quick prediction of radon emanation rate from the ore body.


Outpatient hemithyroidectomy: A retrospective feasibility analysis.
Outpatient surgery is a major public health policy issue. It is controversial for total thyroidectomy, which raises the question of hemithyroidectomy. The present study assessed our experience in outpatient hemithyroidectomy. To evaluate the rates of postoperative hematoma and unscheduled hospital admission. A multicenter retrospective analysis was conducted in two hospital centers between January 2009 and December 2013. Exclusion criteria for outpatient hemithyroidectomy comprised: ASA score >2, anticoagulant therapy, risk of completion procedure, and associated procedure requiring >12 hours' surveillance. Data were collated for age, gender, weight, postoperative complications, and unscheduled hospital admission. During the study period, 294 hemithyroidectomies were performed, 130 of which on an outpatient basis (44%). There were no medical contraindications to outpatient surgery in 64% of patients operated on under conventional admission. In the outpatient group, mean age was 44 years. Eight completion thyroidectomies were performed in the outpatient group, and only two patients required admission for surveillance, with no revision surgeries. All patients were satisfied or very satisfied with outpatient management. In our experience, outpatient hemithyroidectomy was safe and reliable.


Retracted: Analysis of the Effect of Holistic Nursing in the Operating Room Based on PDCA and Evidence-Based Nursing in the Otorhinolaryngology Operating Room: Based on a Retrospective Case-Control Study.
[This retracts the article DOI: 10.1155/2022/4514669.].


Data on megakaryocytes in the bone marrow of mice exposed to formaldehyde.
Previously, we reported that occupational exposure to formaldehyde (FA) exposure in factory workers reduced platelet counts, http://dx.doi.org/10.1158/1055-9965.EPI-09-0762[1], while exposure in mice increased platelet counts http://dx.doi.org/10.1371/journal.pone.0074974[2]. Bone marrow megakaryocyte (MK) numbers were also increased in exposed mice, as determined qualitatively. The data presented here are from a quantitative evaluation of MK numbers in the bone marrow histopathological slides from the previous FA exposure experiments in mice. Bone marrow slides were prepared using a single 5 μm section of femur from 2 mice randomly selected from each exposure group (n=9) treated with 0, 0.5 and 3.0 mg/m(3) FA by nose-only inhalation. MKs were systemically counted and average MK frequency was calculated as the total MK per slide divided by the number of fields evaluated. Data are presented visually as microscopy views and graphically as MK frequency.


Methods for Predicting Potential Impacts of Pile-Driving Noise on Endangered Sturgeon During Bridge Construction.
The potential impacts of pile-driving noise on Hudson River sturgeon during construction of the New NY Bridge were predicted. Abundance data for shortnose and Atlantic sturgeon derived from fisheries sampling were combined with data about the spatial extent of pile-driving noise. This approach was used to calculate the number of sturgeon that could occur within sound level isopleths exceeding peak and cumulative noise criteria used by the National Marine Fisheries Service to determine the incidental take of sturgeon. The number of sturgeon subject to the potential onset of physiological effects during pile driving was predicted to be 35-41 fish for each species.


Hyperreactivity of mediator-releasing cells from patients with allergic bronchopulmonary aspergillosis as evidenced by basophil histamine release.
Histamine release was performed on 28 patients with allergic bronchopulmonary aspergillosis (ABPA) in various stages and on 14 patients with mold-sensitive asthma, by using Aspergillus antigens, other mold antigens, and anti-IgE. Total serum IgE, IgE and IgG antibodies to Aspergillus fumigatus (Af), and end point cutaneous titration for Af were determined for each patient. There was greater histamine release to Aspergillus mix (p = 0.0000) and anti-IgE (p = 0.047) in patients with ABPA than in patients with mold-sensitive asthma. Patients with stages IV and V ABPA had greater histamine release to Aspergillus mix than patients with stage I, II, or III ABPA (p = 0.0014). There was greater histamine release to other molds in ABPA patients than in mold-sensitive asthmatics. There was no correlation between histamine release to Aspergillus mix and total serum IgE, IgE or IgG antibodies to Af, ratio of IgE and IgG antibodies to Af to total IgE, or cutaneous end point titration for Af in ABPA patients or mold-sensitive asthmatics. Peripheral basophils from ABPA patients demonstrated marked hyperreactivity as evidenced by histamine release to Aspergillus antigens, other molds, and anti-IgE. This hyperreactivity is the first cellular difference recognized in ABPA patients when compared to mold-sensitive asthma patients. If this hyperreactivity is manifested by mediator release from other cells such as pulmonary mast cells, which would be in close contact with growing Af, a possible mechanism for pulmonary response in ABPA would be suggested.


Prospective, randomized, back-to-back trial evaluating the usefulness of i-SCAN in screening colonoscopy.
The newly developed i-SCAN application can theoretically maximize the effectiveness of colonoscopy. However, the practical usefulness of the i-SCAN application during screening colonoscopy has not been assessed. To assess the efficacy of the i-SCAN application during screening colonoscopy. A prospective, randomized trial that used a modified, back-to-back colonoscopy. Academic hospital. This study involved 389 asymptomatic, consecutive, average-risk patients who underwent screening colonoscopy. The patients were randomized to the first withdrawal with either conventional high-definition white light (HDWL group; n = 119), i-SCAN contrast/surface enhancement (CE/SE) mode (i-SCAN1 group; n = 115), or i-SCAN CE/SE/tone enhancement-colorectal mode (i-SCAN2 group; n = 118). All patients underwent a second examination with HDWL as the criterion standard. The primary outcome measurement was the adenoma detection rate and adenoma miss rate. The secondary outcome measurement was the accuracy of the histologic prediction of neoplastic and nonneoplastic polyps. The adenoma detection rates during the first withdrawal of HDWL, i-SCAN1, and i-SCAN2 were 31.9%, 36.5%, and 33.1%, respectively (P = .742), and the adenoma miss rates of each group were 22.9%, 19.3%, and 15.9%, respectively (P = .513). Based on the multivariate analysis, the application of i-SCAN was not associated with an improvement in adenoma detection and the prevention of missed polyps. However, the prediction of neoplastic and nonneoplastic colorectal lesions was more precise in the i-SCAN2 group compared with the HDWL group (accuracy 79.3% vs 75.5%, P = .029; sensitivity 86.5% vs 72.6%, P = .020; and specificity 91.4% vs 80.6%, P = .040). Single-center trial. i-SCAN during the screening colonoscopy may fail to improve adenoma detection and the prevention of missed polyps, but i-SCAN appears to be effective for real-time histologic prediction of polyps compared with conventional HDWL colonoscopy. ( NCT01417611.).


The use of PRP in treatment of Achilles Tendinopathy: A systematic review of literature. Study design: Systematic review of literature.
Chronic Achilles Tendinopathy is a common condition that can be challenging to treat. There are many modalities used as treatment ranging from physiotherapy, injections, shockwave therapy to surgical intervention. Platelet Rich Plasma (PRP) has increased in popularity recently as a treatment option for Achilles Tendinopathy. It contains growth factors that might accelerate healing and speed up the recovery of this condition. Many studies have been conducted in the last few years to assess the effectiveness of this treatment method. However, there was controversy as to whether PRP had a beneficial effect on chronic Achille tendinopathy. This systematic review of the literature was conducted to ascertain the efficacy of Platelet Rich Plasma (PRP) as a treatment option in chronic Achilles tendinopathy. PRISMA reporting item for systematic review has been used to conduct the selection, Electronic databases included PubMed, EMBASE, Cochrane collaborate, Google scholar, the web of science and Cochrane Library were searched for all RCT, prospective and retrospective studies conducted between January 2010 to February 2019. The quality of each study was evaluated using the Oxford CEBM tool to assess the articles for validity, relevance, and applicability of the results. A total number of 288 were found, and only 11 met the inclusion criteria. 5 Randomised control trials, 4 prospective and 2 retrospective cohort study were included in this systematic review. A total number of 406 patients were treated for non-insertional Achilles tendinopathy of which 230 patients had PRP local injection under Ultrasound guide. Although many of the retrospective studies suggested an advantage of using PRP, the higher level of evidence studies do not support a significant efficacy. This systematic review showed very promising results from the use of Platelet Rich Plasma demonstrated by a significant improvement in the VAST-A score, but we certainly need decent size randomised control trials to show better and more accurate results.


Determination of daily dietary intake of chromium by duplicate diet sampling: in vitro availability study.
Intake of chromium was estimated using a duplicate diet sampling method of 108 meals (36 breakfasts, 36 lunches and 36 dinners) from the restaurant of the Hospital of Motril (S.E. Spain), corresponding to 36 consecutive days. Total and dialyzable Cr levels were measured by a validated electro-thermal atomic absorption spectrometry (ETAAS) method. A mean Cr fraction of 26 +/- 12 microg meal (-1) was found. The Cr uptake from meals was directly and significantly (p < 0.001) correlated with their macronutrient (carbohydrates, fibre and protein) content. Cereals and cereal by-products, legumes, dry fruits, meat, potatoes, dairy products and seafood are the primary sources of Cr. The mean Cr fraction dialyzed through dialysis tubing was 1.2 +/- 1.1 microg meal(-1) (4.6 +/- 3.8% as mean Cr dialysability). Cr intake for breakfasts was significantly lower (p < 0.001). A correlation between the logarithmic data of total and dialyzable fraction of Cr in meals (p = 0.020) was found and dialysis ratio enhancement and, therefore, bioavailability increased with total Cr. The dialysed element content present in meals was significantly correlated with fibre, protein, Fe, Na, I, F, sodium, ascorbic acid and vitamin A levels (p < 0.05). At Fe contents in meals higher than congruent with7.5 mg meal(-1) the net absorption of Cr decreased significantly. The mean Cr daily dietary intake (DDI) was 77 +/- 17 microg day (-1) which indicates that no adverse effects in relation to Cr nutrition (deficiency or toxicity) should occur in individuals from the area.


Results of an early hearing detection program.
Neonatal hearing loss is a public health problem that meets the requirements for submission to universal screening. Our objective was to analyse the results of the early hearing detection and intervention program implemented at our centre between January 2007 and December 2010. We studied 26,717 newborns during the period mentioned, using transient otoacoustic emissions (TOAEs) for the screening. The diagnostic phase was carried out at the hearing loss department. In our area, there were 27,935 births between January 2007 and December 2010. The screening was performed on 26,717 children. Of these, 24,173 had positive TOAEs, 1,040 had no TOAEs and 1,504 presented TOAEs in 1 ear with absence of TOAEs in the contralateral ear. Risk factors associated with hearing loss were found in 4,674 infants. In a second phase of the program, TOAEs were given to 5,156 children, of whom 4,626 had positive otoacoustic emissions in both ears, 323 had no TOAEs in 1 ear and 207 failed this second phase. Of all children studied, 3.8% were referred to auditory brainstem response (ABR) testing and 26 children entered the cochlear implant program. The program reached coverage of 95.64%. The early hearing detection and intervention program at our hospital is suitable for our environment, reaching 95.64% of coverage. We consider the relationship between effectiveness and efficiency to be positive.


[An experimental study of local chemotherapy for metastatic lung tumor--isolated lung perfusion and pulmonary artery infusion].
We evaluated the efficacy of local chemotherapy using isolated lung perfusion (ILP) and pulmonary artery infusion (PAI) in vivo to improve prognosis for patients with metastatic lung diseases. Male F344 rats were used. The left lung was isolated and chemotherapeutic agents were administrated to the isolated lung by the ILP or PAI technique. Agents used were cisplatin (CDDP) and fluorouracil (5-FU), and their levels in the perfused lung and serum were measured (renal levels were also measured in CDDP groups). The results were compared with those obtained following intravenous administration (i.v.). In the ILP group, the left pulmonary artery and vein were clamped during perfusion. The agents were infused from the pulmonary artery, and the perfusate was collected from the pulmonary venotomy site following flushing with saline before declamping. In the PAI group, the left pulmonary artery was clamped and perfused with 0.2 ml of the agents, pulmonary arterial flow was occluded for 20 minutes, and perfusate was not collected. Rats were sacrificed 5 minutes after declamping in both groups, and the perfused lung and blood (and also kidneys in the CDDP group) were collected for pharmacokinetic examination. Histological examination of the perfused lung was also performed. In the ILP group treated with 1 mg of CDDP and PAI group treated with 0.1 mg of CDDP administration, the lung CDDP levels were significantly higher and the serum and renal CDDP levels were significantly lower than those in the IV group. In the ILP group treated with 150 mg of 5-FU and PAI group treated with 10 mg of 5-FU, the lung 5-FU levels were significantly higher than those in all IV groups and the serum 5-FU levels were lower than those in the IV group treated with 10 mg and 15 mg of 5-FU. The bronchopulmonary construction was histologically maintained in the perfused lung in each group. We concluded that local chemotherapy using ILP or PAI could be a safe and effective choice of therapy, and this method may be clinically applicable.


Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
The PARKIN ubiquitin ligase (also known as PARK2) and its regulatory kinase PINK1 (also known as PARK6), often mutated in familial early-onset Parkinson's disease, have central roles in mitochondrial homeostasis and mitophagy. Whereas PARKIN is recruited to the mitochondrial outer membrane (MOM) upon depolarization via PINK1 action and can ubiquitylate porin, mitofusin and Miro proteins on the MOM, the full repertoire of PARKIN substrates--the PARKIN-dependent ubiquitylome--remains poorly defined. Here we use quantitative diGly capture proteomics (diGly) to elucidate the ubiquitylation site specificity and topology of PARKIN-dependent target modification in response to mitochondrial depolarization. Hundreds of dynamically regulated ubiquitylation sites in dozens of proteins were identified, with strong enrichment for MOM proteins, indicating that PARKIN dramatically alters the ubiquitylation status of the mitochondrial proteome. Using complementary interaction proteomics, we found depolarization-dependent PARKIN association with numerous MOM targets, autophagy receptors, and the proteasome. Mutation of the PARKIN active site residue C431, which has been found mutated in Parkinson's disease patients, largely disrupts these associations. Structural and topological analysis revealed extensive conservation of PARKIN-dependent ubiquitylation sites on cytoplasmic domains in vertebrate and Drosophila melanogaster MOM proteins. These studies provide a resource for understanding how the PINK1-PARKIN pathway re-sculpts the proteome to support mitochondrial homeostasis.