Chest radiograph-based algorithm for managing malfunctioning ports.
To evaluate a chest x-ray-based algorithm for managing malfunctioning ports. A review of interventional radiology procedures on malfunctioning ports during the period 2000-2012 was performed. Events were divided into two periods: before and after implementation of an algorithm beginning with tip position evaluation using a chest x-ray. Time to return to usability, frequency of interventions to restore function, and frequency of malfunctioning ports remaining in use after the procedure were calculated. The review included 303 procedures before implementation of the algorithm on 237 access sites in 227 patients (mean age, 56 y; 38% male) and 155 procedures after implementation of the algorithm on 131 access sites in 130 patients (mean age, 55 y; 35% male). Implementation of the algorithm was associated with significantly fewer repeat checks on the same access (27% before algorithm, 9% after algorithm, P < .001) and reduced frequency of a malfunctioning port remaining in use after the interventional radiology procedure (43% before algorithm to 14% after algorithm, P < .001). Median time from consultation to revision was significantly less after implementing the algorithm (13 days before algorithm, 1 day after algorithm, P < .001). Median time from consultation to port usability was also less after implementing the algorithm (2.7 days before algorithm, 1 day after algorithm, P < .001). Implementation of the algorithm was associated with significantly less frequent repeat procedures on the same port and a lower frequency of malfunctioning ports remaining in place. Use of the algorithm was associated with significantly reduced time from consultation to revision and to return to usability. These findings suggest the algorithm allows triage of patients with malfunctioning ports to the appropriate intervention before undergoing a procedure.


Endoscopically-Associated Hairline Approach to Excision of Second Branchial Cleft Cysts.
To improve the treatment outcome and post-operation rehabilitation of patients with second branchial cleft cysts (SBCC), 46 patients were operated for SBCC. 22 patients were operated by conventional approach, 22 patients were operated by original occipital hairline approach and 2 patients were operated via axillary approach. Assessment of intra-operation and post-operation complications was done and comparative evaluation of the preparations of the morphological structure in the main and reference group I was conducted. Clinical psychological assessment was performed in the post-operation period. Based on the clinical criteria and morphological method, the authors made conclusions on the benefits of the proposed approach to the excision of SBCC and determined indications and contraindications to endoscopically-associated surgery via the proposed approach. Comparative analysis of beneficial outcome clinically significant criteria of the conventional, axillary and proposed original approaches showed differences in the following criteria: "average operation time", "average wound dressing duration", "average duration of hospitalization" and "subjective satisfaction with incision scar". There were no differences revealed in the criteria "average incision length". The proposed approach allowed the authors to shorten the treatment duration and to accelerate the patients port-operation recovery. Due to the proposed approach, the incision opened the fascial layer where the cyst was located. The dissection was performed along the hairline and did not involve upper and lower located layers. Minimal surgery traumatic rate of the proposed approach was proved by the morphological studies.


Clothing up DNA for all seasons: Histone chaperones and nucleosome assembly pathways.
In eukaryotes, the packaging of DNA into chromatin is essential for cell viability. Several important DNA metabolic events require the transient disruption of chromatin structure, but cells have evolved a number of elaborate pathways that operate throughout the cell cycle to prevent the deleterious effects of chromatin erosion. In this review, we describe a number of distinct nucleosome assembly pathways that function during DNA replication, transcription, cellular senescence and early embryogenesis. In addition, we illustrate some of the physiological consequences associated with defects in nucleosome assembly pathways.


Standardization of a 89Sr solution from a BIPM intercomparison using a liquid scintillation method.
A procedure to standardize 89Sr (as strontium chloride) solutions, within the frame of a BIPM intercomparison, by the CIEMAT/NIST method was presented for Instagel Plus, HiSafe III and Ultima Gold liquid scintillation cocktails. The stability was studied for two types of samples: those obtained by direct addition of the 89Sr solution and those by the extra addition of 0.5 ml of HCl (0.1 mol l(-1)) to the cocktails. The results only showed good stability with the three scintillants used when additional HCl was added to the cocktails. The activities per unit mass determined for 89Sr were: 26.344 kBq g(-1) for Instagel Plus; 26.335 kBq g(-1) for HiSafe III; and 26.310 kBq g(-1) for Ultima Gold (at a reference time of 2000.10.01, 00 h UT) with a total uncertainty of 0.5% in each case (k = 1).


An improved LC-MS/MS method for the simultaneous determination of pyrazinamide, pyrazinoic acid and 5-hydroxy pyrazinoic acid in human plasma for a pharmacokinetic study.
In the present work the plasma levels of PZA and its two active metabolites, pyrazinoic acid (PA) and 5-hydroxy pyrazinoic acid (5-OH PA) were determined by a sensitive and rapid LC-MS/MS method. The analytes and their labeled internal standards were extracted from 200μL plasma samples by liquid-liquid extraction with methyl tert-butyl ether: diethyl ether (90:10, v/v) under acidic conditions. Their separation was achieved on a Zorbax Eclipse XDB C18 (100×4.6mm, 3.5μm) column using methanol and 0.1% acetic acid (65:35, v/v) as the mobile phase within 4.0min. Detection and quantitation were done by multiple reaction monitoring on a triple quadrupole mass spectrometer following the transitions, m/z 124.1→81.1,m/z 125.0→80.9 and m/z 141.0→81.0 for PZA, PA and 5-OH PA respectively in the positive ionization mode. All the analytes were baseline resolved with a resolution factor of 3.3 and 6.4 between PZA and its metabolites, PA and 5-OH PA respectively. The calibration curves were linear from 0.100-30.0μg/mL, 0.03-9.00μg/mL and 0.002-0.600μg/mL for PZA, PA and 5-OH PA respectively with r(2)≥0.9980 for all the analytes. The intra-batch and inter-batch accuracy and precision (% CV) across quality controls varied from 93.5-106.7% and 1.10-4.57 respectively for all the analytes. The mean extraction recovery of PZA, PA and 5-OH PA was 83.7%, 89.2% and 80.8% respectively, which was consistent at higher as well as lower concentration levels. The% change in the stability of analytes under different storage conditions ranged -6.7 to 7.1 for all the analytes. The method was applied to assess the comparative bioavailability of a 500mg PZA test and reference formulation in healthy subjects. The assay reproducibility was also tested by reanalysis of 22 incurred subject samples.


Ultra-performance liquid chromatography coupled with graphene/polyaniline nanocomposite modified electrode for the determination of sulfonamide residues.
An ultra-performance liquid chromatography (UPLC) coupled with graphene/polyaniline (G/PANI)-modified screen-printed carbon electrode was developed for separation and sensitive determination of eight sulfonamides (SAs) in shrimp. Electrospraying was selected for electrode modification because it can generate the well dispersion of G/PANI nanocomposites on the electrode surface. Prior to electrochemical detection, eight SAs were completely separated within 7 min by using reversed phase UPLC (C4) with mobile phase containing 70:25:5 (v/v/v) of potassium hydrogen phosphate (pH 3):acetonitrile:ethanol. For amperometric detection, the detection potential acquired from hydrodynamic voltammetry was found to be +1.4V. Under optimal conditions, a wide linearity and low limit of detection were obtained for eight SAs in the range of 0.01-10 µg mL(-1) and 1.162-6.127 ng mL(-1), respectively. Compared to boron-doped diamond (BDD) electrode, a G/PANI-modified screen-printed carbon electrode offered higher sensitivity with lower operating cost. To determine SAs in shrimp samples, solid-phase extraction was used to clean up and preconcentrate the samples prior to UPLC separation. To validate this developed method, a highly quantitative agreement was accomplished with UPLC-UV system. Thus, this proposed system might be an alternative approach for rapid, inexpensive, and sensitive determination of SAs in shrimps.


Advanced adenoid cystic carcinoma of the skull base - The role of surgery.
Adenoid cystic carcinoma (ACC) is a salivary gland malignancy with a propensity for perineural spread and diffuse soft tissue infiltration. In the head and neck this unique biological behaviour can result in skull base involvement. A lack of consensus regarding management of ACC involving the skull base in conjunction with the technical and reconstructive challenges of oncological resection in this region has led to variation in practice between institutions. Retrospective multicentre review of patients with advanced ACC infiltrating the skull base, treated surgically by the Queensland Skull Base Unit between 2005 and 2017, with a minimum follow up time of 24 months. 32 patients were treated for ACC with skull base involvement with oncological resection and post-operative radiation in the study period with a median follow up of 82.18 months (33.11-159.53 months). 5 and 10 year locoregional control were both 88.2% (95% CI 67.5-96.1) despite a high rate of microscopically positive margins (81.3%). Metastatic disease rates were high, resulting in low rates of disease free survival (DFS) (53.0% at 5 years (95% CI 33.7-69.0) and 23.0% at 10 years (9.5-39.8)). Overall survival (OS) was high (5 year 91.8% (95% CI 71.1-97.9), 10 year 63.7% (95% 37.5-81.2)), despite the advanced nature of disease. High rates of locoregional control can be achieved in skull base ACC with oncological resection of disease and post-operative radiation. Whilst disease recurrence rates are high, a majority of recurrence is metastatic and does not confer poor intermediate term overall survival.


Right Case, Right Time: Which Procedures Best Differentiate General Surgery Trainees' Operative Performance?
Assessing surgical trainee operative performance is time- and resource-intensive. To maximize the utility of each assessment, it is important to understand which assessment activities provide the most information about a trainee's performance. The objective of this study is to identify the procedures that best differentiate performance for each general surgery postgraduate year (PGY)-level, leading to recommendations for targeted assessment. The Society for Improving Medical Professional Learning (SIMPL) operative performance ratings were modeled using a multilevel Rasch model which identified the highest and lowest performing trainees for each PGY-level. For each procedure within each PGY-level, a procedural performance discrimination index was calculated by subtracting the proportion of "practice-ready" ratings of the lowest performing trainees from the proportion of "practice-ready" ratings of the highest performing trainees. Four-quadrant plots were created using the median procedure volume and median discrimination index for each PGY-level. All procedures within the upper right quadrant were considered "highly differentiating, high volume" procedures. This study was conducted across 70 general surgical residency programs who are members of the SIMPL collaborative. A total of 54,790 operative performance evaluations of categorical general surgery trainees were collected between 2015 and 2021. Trainees who had at least 1 procedure in common were included. Procedures with less than 25 evaluations per training year were excluded. The total number of evaluations per procedure ranged from 25 to 2,131. Discrimination values were generated for 51 (PGY1), 54 (PGY2), 92 (PGY3), 105 (PGY4), and 103 (PGY5) procedures. Using the above criteria, a total of 12 (PGY1), 15 (PGY2), 22 (PGY3), 21 (PGY4), and 28 (PGY5) procedures were identified as highly differentiating, high volume procedures. Our study draws on national data to identify procedures which are most useful in differentiating trainee operative performance at each PGY-level. This list of procedures can be used to guide targeted assessment and improve assessment efficiency.


Retrograde flexible intramedullary nailing in children's femoral fractures.
We treated 31 femoral shaft fractures in 28 children with a mean age of 6.7 (5-10) years with retrograde flexible intramedullary nailing. There were 16 isolated fractures, while 12 children had associated injuries. The average time for union was 10.5 weeks and there were no delayed unions. There was one broken nail requiring change of treatment, but no infection or refractures. At follow-up after a mean time lapse of 27 months there was no limb-length inequality exceeding 1 cm and no malunion. We feel that femoral fractures in patients aged 5-10 years can be safely treated with retrograde flexible intramedullary nailing with minimal risk of surgical complications.


[Ultrastructural study of posttraumatic regeneration of muscle tissue in adult rats].
Regeneration of muscle fibers in pubertal rats (days 8 and 10 after mechanical trauma) can be followed until the occurrence of muscle tubules, resembling tissue formation during embryogenesis. Apart from the cellular type regeneration, the contractile apparatus recovery was also observed inside the preserved basal-sarcolemmal skirts according to the type of intracellular reparative regeneration.


Expression of serine/glycine metabolism-related proteins is different according to the thyroid cancer subtype.
The aim of this study was to investigate the expression and clinical implications of proteins related to serine/glycine metabolism in different subtypes of thyroid cancer. Tissue microarray (TMA) was constructed with tissues from 557 thyroid cancers, consisting of 244 papillary thyroid carcinomas (PTC), 112 follicular carcinomas (FC), 70 medullary carcinomas (MC), 23 poorly differentiated carcinomas (PDC), and 8 anaplastic carcinomas (AC). Immunohistochemical staining of the serine/glycine metabolism-related molecules phosphoglycerate dehydrogenase (PHGDH), phosphoserine aminotransferase, (PSAT), phosphoserine phosphatase (PSPH), serine hydromethyl transferase (SHMT), and glycine decarboxylase (GLDC) was performed with the TMA blocks and the results were analyzed together with clinicopathologic parameters. The expression of serine/glycine metabolism-related proteins differed among thyroid cancer subtypes. The expression rate of PHGDH (p < 0.001), PSAT1 (p = 0.001), PSPH (p = 0.008), and tumoral SHMT1 (p < 0.001) was higher in PDC and PTC (78.3, 21.7, 21.7, 30.4 and 63.4, 18.6, 12.8, 31.4 %, respectively), and lowest in MC (15.7, 1.4, 0.0, 10.0 %). Stromal SHMT1 expression was highest in AC (62.5 %) and absent in all FC (p < 0.001). In PTC, positivity for PSPH (p = 0.041), tumoral SHMT1 (p = 0.018), and stromal SHMT1 (p < 0.001) expression was higher in the conventional type compared to follicular type (14.1 versus 2.5 %, 33.6 versus 15.0 %, 42.1 versus 10.0 %, respectively). BRAF V600E mutation was associated with a higher rate of PHGDH (p < 0.001), PSAT1 (p = 0.001), PSPH (p < 0.001), tumoral SHMT1 (p = 0.001), stromal SHMT1 (p < 0.001), and GLDC (p < 0.001) expression compared to non-mutant cases (73.5 versus 40.6 %, 23.1 versus 8.5 %, 17.6 versus 1.9 %, 37.0 versus 18.9 %, 45.8 versus 21.7 %, 21.8 versus 6.6 %, respectively). In univariate analysis, stromal SHMT1 expression was associated with shorter disease-free survival (p = 0.015) in follicular variant PTC, and GLDC positivity was associated with shorter overall survival (OS) in sclerotic stromal type (p = 0.002). In FC, minimally invasive type, PSPH positivity correlated with shorter OS (p = 0.045) and in MC, PHGDH positivity correlated with shorter OS (p = 0.034). The expression of serine/glycine metabolism-related proteins differs among different thyroid cancer types, with a higher rate of expression in PDC and PTC, and lower rate of expression in MC. In PTC, the rate of expression is lower in the follicular variant and higher in cases with BRAF V600E mutation.


A systematic review and meta-analysis of risk factors associated with atopic dermatitis in Asia.
Atopic dermatitis (AD) is a chronic, inflammatory skin disorder characterised by intense itch and eczematous lesions. Rising prevalence of AD has been observed worldwide including in Asia. Understanding the risk factors associated with AD may explain its pathogenicity and identify new preventive strategies and treatments. However, AD-associated risk factors and comorbidities specific to Asia have not been systematically reviewed. We performed a systematic review in accordance with the Preferred Reporting Item for Systematic Review and Meta-Analyses (PRISMA) guidelines and summarised epidemiological studies investigating personal, family, and environmental factors and comorbidities associated with AD in Asia. Significant factors were assessed if they can be altered through lifestyle practices and further classified into non-modifiable and modifiable factors. Meta-analysis using the random-effect model was also conducted to provide an overall estimate for several significant factors. We identified a total of 162 epidemiological studies conducted in Asia. Among non-modifiable factors, a family history of atopic diseases was the most reported, suggesting the involvement of genetics in AD pathogenesis. Among modifiable factors, the results of meta-analyses revealed maternal smoking as the strongest risk factor with a pooled odds ratio (OR) of 2.95 (95% CI, 2.43-3.60), followed by active smoking (pooled OR, 1.91, 95% CI, 1.41-2.59). While a family history may aid clinicians in identifying high-risk individuals, literature has long suggested the importance of gene-environment interaction. This review identified several modifiable factors including medical treatments, indoor and outdoor environmental exposure, and personal and family lifestyle specific to Asia. Based on the meta-analyses performed, prevention strategies against AD may start from changing personal and family lifestyle choices, especially smoking habits.


Interpretation of the small-angle X-ray diffraction of collagen in view of the primary structure of the alpha1 chain.
The small-angle X-ray diffraction pattern of collagen has been calculated using the sequence of the alpha 1 chain and a Hodge-Petruska scheme for the packing of the collagen molecules. The molecular stagger giving the best fit of calculated-to observed structure factors has been found to be 236 or 237 amino acid residues for three tendon collagens. But this result depends on the appoximation that the molecular conformation is uniform throughout the molecule. A comparison of the observed and calculated electron density profiles in axial projection leads to a corrected model, in which the COOH-terminal telopeptide is contracted in a way suggesting a saddle-shaped electron density distribution near the collagenase site.


Impact of diabetes mellitus and its complications: survival and quality-of-life in critically ill patients.
Diabetes mellitus represents an increasing problem for patients and health care systems worldwide. We sought to investigate the effect of diabetes and its associated comorbidities on long-term survival and quality of life following an admission to a medical intensive care unit (ICU). A total of 6662 consecutive patients admitted to ICU between 2004 and 2009 were included (patients with diabetes n=796, non-diabetic patients n=5866). The primary endpoint of the study was death of any cause. Data on mortality was collected upon review of medical records or phone interviews. Moreover, a questionnaire was sent to 500 randomly selected patients addressing Health related Quality of Life (HrQoL) after ICU treatment. Overall mortality did not differ significantly between diabetic and non-diabetic patients after ICU treatment (mean follow-up time: 490 days). For a subgroup of patients already exhibiting comorbidities associated with diabetes, the mortality rate was significantly higher (p=0.022). Regarding quality of life, no differences were found between groups. Diabetes was not associated with increased mortality or reduced quality of life in a general population of medical ICU patients. However, once comorbidities associated with diabetes occurred, the survival rate of patients with comorbidities associated with hyperglycemia was significantly reduced.


Persistence with overactive bladder pharmacotherapy in a Medicaid population.
The management of chronic conditions, such as overactive bladder (OAB), is often limited by lack of patient adherence to medication. This article compares persistence rates among Medicaid patients who were prescribed 1 of 3 drugs for treatment of OAB: 2 long-acting agents with once-daily dosing, tolterodine tartrate extended-release capsules (tolterodine ER) and oxybutynin chloride extended release (oxybutynin ER), and oxybutynin immediate release (oxybutynin IR), requiring 3 tablets daily. The study population was comprised of continuously enrolled Medicaid managed care patients filling prescriptions for tolterodine ER, oxybutynin ER, or oxybutynin IR between January 1, 2000, and December 31, 2003. Patients taking any OAB drug in the first 6 months of their observed period of enrollment were excluded to capture new users only. Using survival analyses adjusted for age, sex, and race, the rates of persistence by drug were analyzed. Possession time, the degree to which patients keep medication available even though they may not be taking it daily as prescribed, was also measured. Of 1637 patients (75% women, 45% African American, 26% younger than 18 years of age), 182 were started on tolterodine ER, 215 on oxybutynin ER, and 1240 on oxybutynin IR. Only 32% of those taking oxybutynin IR and 44% of those taking either long-acting agent remained adherent past 30 days. Of those remaining after 30 days, the risk of nonadherence was higher for oxybutynin ER than for tolterodine ER (hazard ratio = 1.47; 95% confidence interval, 1.01-2.14). Persistence rates are better for patients taking drugs with once-daily dosing, but there is a need for a better understanding of non-persistent patients.


Single-site modifications of half-ligated hemoglobin reveal autonomous dimer cooperativity within a quaternary T tetramer.
The patterns of energetic response elicited by single-site hemoglobin mutations and chemical modifications have been determined in order to probe the dimer-dimer interface of the half-ligated tetramer (species [21]) that was previously shown to behave as allosterically distinct from both the unligated and fully ligated molecules. In this study the free energies of quaternary assembly (dimers to tetramers) were determined for a series of 24 tetrameric species in which one dimeric half-molecule is ligated (cyanomet hemes) while the adjacent alpha beta dimer is unligated and contains a single amino acid modification. Assembly energies have also been determined for tetramers bearing the same amino acid modifications but where the hemesites were completely vacant and additionally where they were fully occupied. A total of 72 molecular species were thus characterized. It was found that mutationally induced perturbations to the free energy of quaternary assembly were identical for the half-ligated tetramers and the unligated tetramers over the entire spatial distribution of altered sites, but exhibited a radically different pattern from that of the fully ligated molecules. These results indicate that the dimer-dimer interface of the half-ligated tetramer (species [21]) has the same quaternary structure as that of the unligated molecule, i.e., "quaternary T." This quaternary structure assignment of species [21] strongly supports the operation of a Symmetry Rule which translates changes in hemesite ligation into six T-->R quaternary switchpoints. Analysis of the observed Symmetry Rule behavior in relation to the measured distribution of cooperative free energies for the partially ligated species reveals significant cooperativity between alpha and beta subunits of the dimeric half-tetramer within quaternary T. The mutational results indicate that these interactions are not "paid for" by breaking or making noncovalent bonds at the dimer-dimer interface (alpha 1 beta 2). They arise from structural and energetic changes that are "internal" to the ligated dimer even though its association with the unligated dimer is required for the cooperativity to occur. Free energy of "tertiary constraint" is thus generated by the first binding step and is propagated to the second hemesite while the dimer-dimer interface alpha 1 beta 2 serves as a constraint. The "sequential" cooperativity that occurs within the half-molecule is thus preconditioned by the constraint of a quaternary T interface; release of this constraint by dissociation produces only noncooperative dimers.(ABSTRACT TRUNCATED AT 400 WORDS)


Transdermal delivery of isosorbide 5-mononitrate from a new membrane reservoir and matrix-type patches.
Isosorbide 5-mononitrate (5-ISMN) has a direct relaxing effect on vascular smooth muscle. In the present study we developed matrix and reservoir-type transdermal patches of 5-ISMN. We investigated the usefulness of a new film-forming material isolated from the roots of Salacia macrosperma to serve as rate-controlling membrane for the reservoir-type patches. Matrix-type patches were formulated using polyvinyl chloride. Permeation studies through rat skin were conducted on both types of patches using Teflon cells. The mean +/- SD flux values from the matrix- and reservoir-type patches were 99.55 +/- 22.89 and 31.82 +/- 8.31 micrograms/cm2.hr, respectively.


A translocation breakpoint disrupts the ASPM gene in a patient with primary microcephaly.
Primary microcephaly (microcephalia vera) is a developmental abnormality resulting in a small brain, with mental retardation. It is usually transmitted as an autosomal recessive trait, and six loci have been reported to date. We analyzed a translocation breakpoint previously reported in a patient with apparently sporadic primary microcephaly, at 1q31, where locus MCPH5 maps. The patient was lost to follow-up, and we sampled a maternal aunt who carried the familial translocation. FISH analyses showed that the insert of BAC clone RP11-32D17 spanned the breakpoint. The breakpoint was further located within a fragment of this insert corresponding to intron 17 of the ASPM gene, resulting in a predicted transcript truncated of more than half of its coding sequence. It is very likely that the proband carried a second ASPM mutation in trans, but he was not available for sampling and hence we could not confirm this hypothesis. Our observation adds to the mutation spectrum of ASPM in primary microcephaly, and is to our knowledge the second example of a constitutional, reciprocal translocation responsible for a bona fide autosomal recessive phenotype.


Optimizing patient selection for stereotactic ablative radiotherapy in patients with locally advanced pancreatic cancer after initial chemotherapy - a single center prospective cohort.
The role of stereotactic ablative radiation therapy (SABR) as local treatment option after chemotherapy for locally advanced pancreatic cancer (LAPC) is evolving. However adequate patient selection criteria for SABR in patients with LAPC are lacking. A prospective institutional database collected data of patients with LAPC treated with chemotherapy, mainly FOLFIRINOX, followed by SABR, which was delivered using magnetic resonance guided radiotherapy, 40 Gy in 5 fractions within two weeks. Primary endpoint was overall survival (OS). Cox regression analyses were performed to identify predictors for OS. Overall, 74 patients were included, median age 66 years, 45.9% had a KPS score of ≥90. Median OS was 19.6 months from diagnosis and 12.1 months from start of SABR. Local control was 90% at one year. Multivariable Cox regression analyses identified KPS ≥90, age <70, and absence of pain prior to SABR as independent favorable predictors for OS. The rate of grade ≥3 fatigue and late gastro-intestinal toxicity was 2.7%. SABR is a well-tolerated treatment in patients with unresectable LAPC following chemotherapy, with better outcomes when applied in patients with higher performance score, age <70 years and absence of pain. Future randomized trials will have to confirm these findings.


H-2 restriction of contact inhibition of epithelial cells.
Medawar has suggested that the major histocompatibility gene complex (MHC) might be involved in the contact inhibition of movement shown by fibroblasts and epithelia. Contact inhibition of movement is that reaction of cells which stops the movement of one cell over another and thus leads to monolayering and other features of morphology typical of cells in culture and in vivo. By confronting epithelial outgrowths we have compared contact inhibition between syngeneic cells with that between allogeneic cells. Contact inhibition was more marked between allogeneic combinations than syngeneic combinations, when the genetic mismatch lay in certain parts of the MHC complex.


Aflatoxicosis, infectious bursal disease and immune response to Newcastle disease vaccination in rural chickens.
To investigate the immunosuppressive effects of infectious bursal disease virus (IBDV) and aflatoxin in indigenous chickens of Uganda, Newcastle disease (ND) seronegative chicks were randomly allocated to two treatment groups. Group A chicks were injected intramuscularly at the age of 3 weeks every 2 days up to four times with 0.250 mg aflatoxin B1 per bird, group B was infected occulo-nasally with IBDV 3 days prior to vaccination, while group C was left as a control group. All the chicks from the three groups were then vaccinated with Hitchner B1 vaccine at 21 days of age followed by a secondary vaccination with La Sota vaccine 3 weeks later. Humoral and cell-mediated immune responses were assessed by measuring antibody levels and delayed hypersensitivity reaction post vaccination. Growth performance in the three groups was assessed by weekly body weights while evidence of excretion of vaccinal ND virus was detected by reverse transcription-polymerase chain reaction.A significant (P < 0.05) reduction in the haemagglutination inhibition of ND antibody titre following initial priming with Hitchner B1 and subsequent booster with La Sota vaccines and a delayed hypersensitivity test following sensitization with dinitrochlorobenzene showed aflatoxin to be a more potent immunosuppressant than IBDV. Aflatoxin exerted its maximum effects during primary antibody response in the second and third weeks post vaccination. Aflatoxin and IBDV did not affect growth rates (P > 0.05) but prolonged La Sota vaccine virus excretion in faeces. Under our experimental conditions, aflatoxin and IBDV do not significantly affect the immune response of rural chickens to ND vaccination.


Immunophenotypic analysis of lymphocyte subsets in newborns with biotinidase deficiency.
Biotin is a vital micronutrient that plays a role in metabolic homeostasis and the regulation of innate and adaptive immune system functions. Biotinidase deficiency (BTD) leads to impairment in biotin-dependent immune functions. This study focused on immunophenotypic analysis of lymphocyte subsets in newborns with BTD. A total of 181 (95 female and 86 male; 114 had BTD and 67 were healthy) newborns underwent biotinidase enzyme activity, molecular and lymphocyte immunophenotyping analyses. BTD is classified into four biochemical phenotypes: profound, partial, heterozygous and normal. The following lymphocyte subsets were studied in all participants: total B lymphocyte (CD19), total T lymphocyte (CD3), helper T lymphocyte (CD3/CD4), cytotoxic T lymphocyte (CTL) (CD3/CD8), natural killer T lymphocyte (CD16/56) and a T-lymphocyte activation marker (HLA-DR). The percentages of lymphocyte subsets were similar in newborns with and without BTD. In all newborns with BTD, the mean CD3/CD4 levels were higher in females, while the CD3/CD8 levels were higher in males (P < .001 for each). In female and male newborns, the CD3/CD4 levels were 53.83 ± 9.46 and 16.82 ± 5.19, respectively, and the CD3/CD8 levels were 48.80 ± 8.65 and 21.48 ± 6.02, respectively. A moderate negative correlation was found between CD3/CD4 and CD3/CD8 in female and male newborns (rfemale = -0.488, rmale = -0.574, P < .001). This study showed that although there were no differences in the lymphocyte subsets in newborns with BTD, the CD3/CD4 levels were higher in females, and the CD3/CD8 levels were higher in males. In addition, there was a negative correlation between the CD3/CD4 and CD3/CD8 levels in both genders. Although these results indicate sexual dimorphism between CD3/CD4 and CD3/CD8 levels, whether this dissociation is unique to BTD in newborns is not fully clear.


Detection of closed influenza virus hemagglutinin fusion peptide structures in membranes by backbone (13)CO- (15)N rotational-echo double-resonance solid-state NMR.
The influenza virus fusion peptide is the N-terminal ~20 residues of the HA2 subunit of the hemagglutinin protein and this peptide plays a key role in the fusion of the viral and endosomal membranes during initial infection of a cell. The fusion peptide adopts N-helix/turn/C-helix structure in both detergent and membranes with reports of both open and closed interhelical topologies. In the present study, backbone (13)CO-(15)N REDOR solid-state NMR was applied to the membrane-associated fusion peptide to detect the distribution of interhelical distances. The data clearly showed a large fraction of closed and semi-closed topologies and were best-fitted to a mixture of two structures that do not exchange. One of the earlier open structural models may have incorrect G13 dihedral angles derived from TALOS analysis of experimentally correct (13)C shifts.


Subclinical riboflavin deficiency is associated with outcome of seriously ill patients.
The biochemical status of 152 patients in the Intensive Therapy Unit (ITU) was examined in relation to their clinical outcome. Patients who died in ITU or within one week of discharge were found to have significantly poorer riboflavin status than those who survived, but the majority of these measurements were within the normal range. Normal ranges established on a healthy population may therefore not be appropriate in investigation of vitamin nutritional status in seriously ill patients. These results do however suggest that riboflavin status is a risk factor in critically ill patients, and that subclinical riboflavin depletion may affect outcome.


Mutagenicity of the mycotoxin diacetoxyscirpenol on somatic and germ cells of mice.
Genotoxicity of diacetoxyscirpenol (DAS) was studied on laboratory mice after intraperitoneal injection with single and repeated doses. DAS was administrated at three different dose levels (0.5, 0.75, and 1.0 mg/kg body weight). The study was conducted on both somatic and germ cells additional to the sperm morphology analysis. DAS treatment resulted in a significant reduction (P<0.01) in mitotic activity at all levels of doses tested, confirming that DAS is a potent protein and DNA synthesis inhibitor. At somatic cells (bone marrow) both structural and numerical chromosome abnormalities were observed. Single dose treatment showed significant abnormalities only with high dose treatment. In contrast, at repeated dose similar abnormalities were also observed with some significance but no systematic relation between the administrated dose and abnormalities ratio could be settled. In germ cells (testicles), structural and numerical abnormalities were also observed. In general, the frequencies of scored abnormalities at germ cells were lower than that the somatic cells. Sperm count test revealed a decrease in the number of released sperm after toxin treatment. Abnormalities of sperm shape (head and tail) were observed, confirming the positive correlation between cytogenetic damage and sperm abnormality.The results also proved that DAS is a very toxic mycotoxin, in addition to inducing chromosomal abnormalities, it causes a severe inhibition of DNA synthesis which subsequently affects the cell cycle and cell division. A good system for good harvesting practice and good food technology can lower the risk for the consumers.


Pulmonary artery hemodynamics with varying degrees of valvular stenosis: an in vitro study.
The study was to investigate the effects of varying degrees of valvular stenosis on the hemodynamics of the main (MPA), left (LPA), and right (RPA) pulmonary arteries. Particle flow visualization was used to examine the flow patterns in a series of pulmonary artery models manufactured out of glass. These glass models were made based on the geometry of the porcine pulmonary arteries with dilatation in the MPA and LPA. Also, detailed pressure mappings in the models were conducted using a side-hole catheter. As the valve became stenotic, a jet-like flow was observed in the M PA. A higher degree of valvular stenosis corresponded to a narrower jet. This jet-like flow was noted to deflect away from the centerline and impinge on the roof of the dilated MPA. Additionally, a notable pressure gradient across the deflected jet-like flow in the direction of its radius of curvature was seen. Moreover, secondary flows started to appear in the dilated MPA. This suggested that the change in geometry in the MPA, due to its dilatation, had a marked effect on the pulmonary artery hemodynamics. In the LPA and RPA, the strengths of the secondary flows increased as the valve became more stenotic. The flow patterns observed in the LPA appeared to be more disturbed than in the RPA, due to the poststenotic, dilatation present in the LPA. Pressure recovery along the axial direction in the M PA was observed for all the stenotic valves studied. As the degree of valvular stenosis increased, the transvalvular energy loss increased. Moreover, it was observed that the energy loss decreased progressively as the flow traveled downstream. This tendency was consistent with the phenomenon of pressure recovery observed in the pressure measurement. The study demonstrates the importance of analyzing biological flows from a three-dimensional viewpoint.


CpG-containing oligodeoxynucleotides act through TLR9 to enhance the NK cell cytokine response to antibody-coated tumor cells.
Bacterial DNA contains a high frequency of unmethylated CpG motifs that stimulate immune cells via TLR9. NK cells express a low-affinity activating receptor for the Fc portion of IgG (FcgammaRIIIa), but were not thought to express TLR9 protein. The direct response of NK cells to CpG oligodeoxynucleotides (ODN) in the presence of FcR stimulation was investigated. Human NK cells cultured in the presence of CpG ODN plus immobilized IgG or Ab-coated tumor cells secreted large amounts of IFN-gamma (>2000 pg/ml), whereas cells stimulated with Ab alone, CpG ODN alone, or Ab and control ODN produced negligible amounts. Enhanced secretion of IL-8, macrophage-derived chemokine, and MIP-1alpha was also observed after costimulation. NK cell cytokine production was not the result of interactions with APCs or their cytokine products. Flow cytometric analysis revealed that 36 +/- 3.5% of human NK cells expressed basal levels of TLR9. TLR9 expression in human NK cells was confirmed by immunoblot analysis. Only TLR9-expressing NK cells responded to CpG ODN and Ab, because cytokine production was not observed in NK cells from TLR9-deficient mice. Mice receiving CpG ODN and HER2/neu-positive tumor cells treated with an anti-HER2 Ab exhibited enhanced systemic levels of IFN-gamma compared with mice receiving either agent alone. TLR9-/- animals reconstituted with TLR9+/+ NK cells secreted IFN-gamma in response to CpG ODN and Ab-coated tumor cells. These findings indicate that CpG ODN can directly enhance the NK cell cytokine response to Ab-coated targets via activation of TLR9.


Favorable Management of Low Colorectal Anastomotic Leakage with Transanal Conventional and Endoscopic Drainage (GelPOINT® Path Transanal Access Platform).
We describe our experience with transanal-laparoscopic treatment of anastomotic leakage. Anastomotic leakage leads to high mortality rates, morbidity, a complicated post-operative course and increased cost. The management of low anastomotic leakage after anterior resection of rectal cancer is not standardized. This was a retrospective cohort study based on prospectively collected data. Among patients who underwent anterior resection for rectal cancer in our division between January 2014 and October 2017, 14 developed colorectal or colo-anal anastomotic leakage and underwent reoperation with a transanal approach. Data regarding patient demographics, reoperative outcomes, morbidity, length of hospital stay, mortality, leak closure and long-term outcomes are presented. In all patients, anastomotic healing was confirmed by radiology. No perioperative complications were detected. One patient presented anastomotic stricture after 20 months, which was successfully treated with dilatation. There is little information available on the management of anastomotic leakage after anterior resection for rectal cancer. Although more studies are needed to standardize patient selection criteria and evaluate the long-term outcome of these procedures, minimally invasive transanal conventional and laparoscopic anastomotic leak repair is a feasible and safe surgical option that can often avoid the need for anastomotic takedown and stoma formation.


Development of 3-PM liquid scintillation counting system with geometrical efficiency variation.
An improved triple-to-double coincidence ratio system has been developed to obtain efficiency variation by means of geometrical displacement, that is, three photomultiplier (PM) tubes move back and forth direction from a vial source. The detection unit of the system is located in a cylindrical chamber for light shielding, and a stepping motor connected to the three PM tubes controls the source-to-detector distance up to 50 mm with 1 mm resolution. In activity measurements of 14C and 204Tl using this measurement technique, the efficiencies varied from 0.60 to 0.90 for 14C and from 0.87 to 0.96 for 204Tl. In this study, the characteristics of the system are described as well as data acquisition and analysis methods.


Organ culture of the postnatal mouse Crista ampullaris. Part I.
The 2 day post partum mouse Crista ampullaris was cultured "in vitro" for 7 days. The differentiation into secretory and sensory areas was preserved. The ultrastructure of the dark cells of the secretory region was well maintained. The hair cell morphologically was considerably changed though the hair cells themselves survived 7 days in culture.


Primary cerebral lymphoma presenting with bilateral cerebellopontine angle lesions.
A case is described of a primary cerebral lymphoma which presented with bilateral cerebellopontine angle lesions. No similar case has been reported in the English language in the last 25 years. The literature is reviewed and discussed.


alpha2-Macroglobulin in the marine fish Sparus aurata.
The alpha2-macroglobulin proteinase inhibitors (alpha2Ms) are a family of plasma proteins with the unique ability to inhibit a broad spectrum of proteinases, but are also known as binding proteins for many growth factors and cytokines, including growth hormone and members of the transforming growth factor-beta superfamily. A partial cDNA (475 amino acids) encoding the C-terminus of alpha2M was cloned from the liver of the marine teleostean fish Sparus aurata. The deduced amino acid sequence of the cloned fragment showed 58-60% similarity to carp alpha2Ms. Northern blot analysis of hepatic alpha2M revealed a transcript of about 5 kb. A transcript of a similar size was detected in 1-day larvae. Steady state levels of alpha2M in larvae increased gradually on subsequent days post-hatching. alpha2M expression in embryos was determined by RT-PCR and started in embryos aged 8 h post-fertilization, but not earlier. RT-PCR of muscle RNA detected alpha2M also in fish muscle, albeit with a lower expression than in the liver. Immunoreactive-alpha2M was found in yolk syncytial layer of 3-day larvae and in livers from larvae and adults. Immunoreactive-alpha2M was also identified in soluble total proteins from young larvae with a pattern resembling that of plasma. These data demonstrate that the alpha2M gene is expressed early in fish development. Moreover, in addition to its major expression in liver, alpha2M is expressed also in fish muscle.


Microbial oxidation of gaseous hydrocarbons. II. Hydroxylation of alkanes and epoxidation of alkenes by cell-free particulate fractions of methane-utilizing bacteria.
Cell-free particulate fractions derived from methylotrophic bacteria catalyze the oxygen- and reduced nicotinamide adenine dinucleotide-dependent epoxidation of alkenes and hydroxylation of alkanes. Evidence presented indicates that the hydroxylation and epoxidation reactions are catalyzed by the same or a similar metal-containing monooxygenase.


[Need for and predictability of magnetic resonance imaging examinations in patients with implanted neurostimulators].
With an increasing number of magnetic resonance imaging (MRI) examinations in the general population, there are no data available regarding the requirements of patients with implanted neurostimulators in Germany. Published data from the United States of America suggest a high need. The limited approval for MRI scans of implants are a common problem. The focus is on the MRI needs of these pain patients and the predictability at the time of implantation. We carried out a retrospective evaluation of the database of our hospital information system. We searched for all MRI requests for patients with an implanted neurostimulator between November 2011 and March 2019. In addition, we compared these data with the implantation of neurostimulators in the same period. We identified 171 MRI examinations and 22 requests without a subsequent examination. Out of 294 (28%) patients implanted in our center 83 had at least 1 MRI scan in our hospital. We observed a steadily increasing demand. In 111 of 171 (65%) performed examinations, there was no association between the indications leading to neurostimulator implantation and to MRI. A predictability could only be assumed for 43 of 193 (22%) MRI requests. In Germany, patients with an implanted neurostimulator have a high need for MRI diagnostics which cannot be predicted at the time of implantation. Therefore, only MRI-conditional systems should be implanted. The manufacturers need to adapt the implants and their approval to requirements.


Distribution patterns and possible influencing factors of As speciation in ornithogenic sediments from the Ross Sea region, East Antarctica.
Ornithogenic sediments are rich in toxic As (arsenic) compounds, posing a potential threat to local ecosystems. Here we analyzed the distribution of As speciation in three ornithogenic sediment profiles (MB6, BI and CC) collected from the Ross Sea region, East Antarctica. The distributions of total As and total P (phosphorus) concentrations were highly consistent in all three profiles, indicating that guano input is a major factor controlling total As distribution in the ornithogenic sediments. The As found in MB6 and CC is principally As(V) (arsenate), in BI As(III) (arsenite) predominates, but the As in fresh guano is largely composed of DMA (dimethylarsinate). The significant difference of As species between fresh guano and ornithogenic sediment samples may be related to diagenetic processes after deposition by seabirds. Based on analysis of the sedimentary environment in the studied sediments, we found that the redox conditions have an obvious influence on the As speciation distribution. Moreover, the distributions of As(III) and chlorophyll a in the MB6 and BI profiles are highly consistent, demonstrating that aquatic algae abundance may also influence the distribution patterns of As speciation in the ornithogenic sediments.


[Spontaneous choroidal hemorrhage associated with novel oral anticoagulants: A report of two cases and literature review].
New direct oral anticoagulants (DOAC) have been approved for treatment and prevention of some thromboembolic diseases: acute and chronic phase of thromboembolic disease, deep venous thrombosis prophylaxis in orthopedic surgery and prevention of stroke in patients with atrial fibrillation. These molecules are an alternative to heparins and vitamin K antagonists. Among these, rivaroxaban (Xarelto®, Bayer Schering Pharma) is a direct factor Xa inhibitor, and dabigatran etexilate (Pradaxa®, Boehringer Ingelheim) is a direct free thrombin inhibitor. These molecules are almost the ideal anticoagulant: oral administration, few drug and food interactions, wide therapeutic target, and especially no lab monitoring. However, their use remains associated with hemorrhagic complications such as gastrointestinal, intracranial or urinary hemorrhages. We describe two clinical cases of spontaneous choroidal hemorrhage in patients treated with direct oral anticoagulants (rivaroxaban and dabigatran etexilate) for atrial fibrillation. These cases show that an ocular hemorrhagic risk exists with these drugs. Patients treated with DOAC should have the therapeutic dose adjusted based on creatinine clearance. Special monitoring should be performed in patients with age-related macular degeneration or with hypertension even though meta-analysis shows that the risk of intraocular bleeding is reduced by 22% compared with warfarin.


Metabolic syndrome: a marker of patients at high cardiovascular risk.
The metabolic syndrome is a constellation of metabolic abnormalities associated with an increased risk for cardiovascular disease (CVD). It is present in one of four adults, and its prevalence is markedly increased in obese adults and adolescents. The plasma concentration of C-reactive protein (CRP), a marker of inflammation, is elevated in obese patients, is correlated with the metabolic syndrome and decreases with weight loss. CRP is produced by mature adipocytes in adipose tissue, and may contribute to the elevated circulating plasma CRP concentrations present in obese patients and people with the metabolic syndrome. Treatment of the metabolic syndrome is aimed at improving insulin resistance through lifestyle changes, namely weight loss and regular physical activity. In patients with abnormal glucose concentrations, dyslipidemia or hypertension, treatment of the individual components of the syndrome may result in greater impact on reducing overall CVD risks. Given the prevalence of the metabolic syndrome and the exaggerated CVD risks, innovative therapeutic approaches continue to evolve.


Association between sleep duration and obesity is modified by dietary macronutrients intake in Korean.
Short sleep duration has been reported to be inversely associated with risk of obesity. The effects of sleep duration on obesity-related variables and the interaction of sleep duration and dietary macronutrients consumption on risk of obesity were analysed in 14,111 subjects aged 20-79 from the Korean National Health and Nutrition Examination Survey. Sleep restriction to less than 7h per day resulted in higher body mass index, plasma triglyceride level, and obesity prevalence for women, but not for men. Protein intake was significantly lower in subjects with lower sleep duration for both men and women. The subjects with short sleep duration were significantly higher fat consumption for men, whereas carbohydrate consumption for women. Among subjects whose carbohydrate consumption was above the median, subjects with sleep duration of less than 7h per day increased their odds of being obese (OR=1.255, 95% CI: 1.073-1.476, P<0.001) compared to subjects with sleep duration more than 7h per day for women. Our results showed that sleep duration positively correlated with protein consumption, but negatively correlated with carbohydrate consumption, which might lead to high risk of obesity for women. Also, our findings support a significant association between sleep duration and obesity-related variables and this association has been potentially modified by dietary macronutrients consumption in women subjects.


Multiply Charged Conjugated Polyelectrolytes as a Multifunctional Interlayer for Efficient and Scalable Perovskite Solar Cells.
A series of anionic conjugated polyelectrolytes (CPEs) is synthesized based on poly(fluorene-co-phenylene) by varying the side-chain ionic density from two to six per repeat units (MPS2-TMA, MPS4-TMA, and MPS6-TMA). The effect of MPS2, 4, 6-TMA as interlayers on top of a hole-extraction layer of poly(bis(4-phenyl)-2,4,6-trimethylphenylamine (PTAA) is investigated in inverted perovskite solar cells (PeSCs). Owing to the improved wettability of perovskites on hydrophobic PTAA with the CPEs, the PeSCs with CPE interlayers demonstrate a significantly enhanced device performance, with negligible device-to-device dependence relative to the reference PeSC without CPEs. By increasing the ionic density in the MPS-TMA interlayers, the wetting, interfacial defect passivation, and crystal growth of the perovskites are significantly improved without increasing the series resistance of the PeSCs. In particular, the open-circuit voltage increases from 1.06 V for the PeSC with MPS2-TMA to 1.11 V for the PeSC with MPS6-TMA. The trap densities of the PeSCs with MPS2,4,6-TMA are further analyzed using frequency-dependent capacitance measurements. Finally, a large-area (1 cm2 ) PeSC is successfully fabricated with MPS6-TMA, showing a power conversion efficiency of 18.38% with negligible hysteresis and a stable power output under light soaking for 60 s.


[The effect of early escheractomy on expression of ICAM-1 and E-selectin mRNA of endothelial cells].
To examine the effect of burned serum on change in endothelial cell ICAM-1 and E-selectin mRNA expression and whether these alterations can be corrected by the means of escharectomy during burn shock period. One hundred and seventy-six Wistar rats with 30% III degree TBSA on back were studied. Endothelial cell ICAM-1 and E-selectin mRNA were tested with the method of RT-PCR. ICAM-1 and E-selectin expression showed an increase after stimulation by serum of 4 hours post burn, reaching peak levels 168 hours after injury. ICAM-1 and E-selectin expression levels could decrease to baseline within 168 hours in the rats which underwent escharectomy during shock stage, but kept higher than normal in rats without escharectomy or underwent 96 hours post burn. These findings suggest that eschar can induce endothelial cells to express adhesion molecule. Early escharectomy is important to prevent adhesion molecule expression and SIRS.


PNC2 (SLC25A36) Deficiency Associated With the Hyperinsulinism/Hyperammonemia Syndrome.
The hyperinsulinism/hyperammonemia (HI/HA) syndrome, the second-most common form of congenital hyperinsulinism, has been associated with dominant mutations in GLUD1, coding for the mitochondrial enzyme glutamate dehydrogenase, that increase enzyme activity by reducing its sensitivity to allosteric inhibition by GTP. To identify the underlying genetic etiology in 2 siblings who presented with the biochemical features of HI/HA syndrome but did not carry pathogenic variants in GLUD1, and to determine the functional impact of the newly identified mutation. The patients were investigated by whole exome sequencing. Yeast complementation studies and biochemical assays on the recombinant mutated protein were performed. The consequences of stable slc25a36 silencing in HeLa cells were also investigated. A homozygous splice site variant was identified in solute carrier family 25, member 36 (SLC25A36), encoding the pyrimidine nucleotide carrier 2 (PNC2), a mitochondrial nucleotide carrier that transports pyrimidine as well as guanine nucleotides across the inner mitochondrial membrane. The mutation leads to a 26-aa in-frame deletion in the first repeat domain of the protein, which abolishes transport activity. Furthermore, knockdown of slc25a36 expression in HeLa cells caused a marked reduction in the mitochondrial GTP content, which likely leads to a hyperactivation of glutamate dehydrogenase in our patients. We report for the first time a mutation in PNC2/SLC25A36 leading to HI/HA and provide functional evidence of the molecular mechanism responsible for this phenotype. Our findings underscore the importance of mitochondrial nucleotide metabolism and expand the role of mitochondrial transporters in insulin secretion.


Autocatalytic maturation of the prohormone convertase PC2.
PC2 is a member of the eukaryotic family of subtilisin-like proteases, which is thought to participate in the processing of prohormones and proneuropeptides in neuroendocrine cells. PC2 is synthesized as a 69-kDa prepropolypeptide. The NH2-terminal signal sequence is removed during segregation within the endoplasmic reticulum, where glycosylation occurs to generate a 75-kDa propolypeptide. A combination of site-directed mutagenesis and a cell-free translation/translocation system from Xenopus eggs was used to investigate the processing of the pro-PC2 precursor. The 75-kDa polypeptide underwent slow cleavage after the sequence Arg-Lys-Lys-Arg84 to generate a 68-kDa mature enzyme. Cleavage was blocked when the tetrabasic sequence was deleted (PC2M3) or when the active site Asp142 was changed to Asn (PC2M4). This latter observation suggested that cleavage of the 75-kDa propolypeptide to the mature 68-kDa enzyme was autocatalytic. Incubation of the PC2M4 mutant with the wild type PC2 precursor resulted in cleavage of both the wild type polypeptide and the catalytically inactive PC2M4 mutant. This indicates that cleavage could occur through an intermolecular reaction. The results also demonstrate that the novel Xenopus egg extract translation/translocation system represents a powerful cell-free method for studying proteolytic processing of propolypeptides.


Convergent Synthesis of 2H-Chromenes - a Formal [3+3] Cycloaddition by a One-pot, Three-Step Cascade.
In cases in which the palladium-catalyzed coupling of a bromoquinone with a vinyl stannane affords a vinyl quinone that enolizes, the resulting ortho-quinone methide undergoes an oxa-6π electrocyclization. Enolization is promoted by the presence of a polar additive. The net conversion is a formal [3+3] cycloaddition that gives 2H-chromenes. Because the first two steps of the cascade are catalyzed, the overall conversion is an example of multicatalysis. Yields for the optimized, one-pot protocol are dramatically improved over the conventional stepwise process.


The pyrimido-pyrimidine derivatives RA 233 and RX-RA 85 affect growth and cytoskeletal organization of rat mammary adenocarcinoma cells.
The pyrimido-pyrimidine derivatives RA 233 and RX-RA 85, which are potent inhibitors of platelet and tumor phosphodiesterase, were developed as antitumor agents. When tested by us, these drugs were cytostatic at low concentrations and produced dramatic changes in cell shape and organization of cytoskeletal structures in cultured MTF7 cells derived from the rat 13762NF mammary adenocarcinoma. At high concentrations (up to 600 micrograms/ml) RA 233 was cytostatic but not cytotoxic to MTF7 cells during a 24 hr incubation in vitro, whereas RX-RA 85 was cytotoxic at concentrations above 4 micrograms/ml. These drugs caused MTF7 cells to elongate and form numerous vacuoles, which surrounded the cell nucleus. Treatment of MTF7 cells with RA 233 or RX-RA 85 enhanced microtubular organization concomitant with a decrease in microfilament organization. In contrast, treatment of MTF7 cells with 1 mM dibutyryl cAMP resulted in an enhanced organization of microtubules but had no effect on microfilament organization. Previous studies suggested that RA 233 and RX-RA 85 increase cAMP levels in 2 other cell clones of rat 13762NF mammary adenocarcinoma by inhibiting phosphodiesterases. However, additional sites of drug action should also be considered based on the effects of these drugs on microfilament systems and cell vacuoles.


[Inner Ear Hearing Loss].
Hearing loss is one of the most dominant handicaps in modern societies, which additionally very often is not realized or not admitted. About one quarter of the general population suffers from inner ear hearing loss and is therefore restricted in communicational skills. Demographic factors like increasing age play an important role as well as environmental influences and an increasing sound and noise exposure especially in leisure activities. Thus borders between a "classical" presbyacusis - if it ever existed - and envirionmentally induced hearing loss disappear. Today restrictions in hearing ability develop earlier in age but at the same time they are detected and diagnosed earlier. This paper can eventually enlighten the wide field of inner ear hearing loss only fragmentarily; therefore mainly new research, findings and developments are reviewed. The first part discusses new aspects of diagnostics of inner ear hearing loss and different etiologies.


Upregulation of protein kinase cdelta in vascular smooth muscle cells promotes inflammation in abdominal aortic aneurysm.
The development of abdominal aortic aneurysms (AAAs) involves a complex interplay of extracellular matrix degradation, inflammation, and apoptosis. We have previously shown that protein kinase Cdelta (PKCdelta) plays a critical role in vascular smooth muscle cell (vSMC) apoptosis in the setting of oxidative stresses. Here, we show that PKCdelta is also involved in the signaling that draws inflammatory cells to aneurismal tissue. Immunostaining for monocyte chemotactic factor (MCP)-1 and PKCdelta was performed on paraffin-fixed arterial sections. Enzyme-linked immunosorbent assay to detect MCP-1 produced by vSMCs was performed on media from cultured rat A10 cells after cytokine induction with or without the PKCdelta-specific inhibitor rottlerin. Migration of isolated lymphocytes was evaluated in response to media from activated A10 cells. Human AAAs show widespread and elevated expression of PKCdelta that is not seen in normal aortic tissues. Cytokine stimulation of cultured vSMCs induced vigorous production of the key chemotactant MCP-1, the expression of which was PKCdelta dependent. Stimulated vSMCs were capable of inducing the migration of leukocytes, and this effect was also dependent on PKCdelta activity. Staining of human AAA tissue for MCP-1 showed an expression pattern that was identical to that of PKCdelta and smooth muscle specific alpha-actin. PKCdelta is widely expressed in human AAA vessel walls and mediates MCP-1 expression by vSMCs, which could contribute to the inflammatory process. These findings, coupled with earlier studies of PKCdelta, suggest that PKCdelta plays a central role in the pathogenesis of AAAs and may be a potential target for future therapies.


Virus isolation and serum antibody responses after infection of cats with transmissible gastroenteritis virus. Brief report.
Transmissible gastroenteritis virus was administered orally to cats. No clinical disease resulted but infectious virus was isolated from faeces for up to 22 days after infection and serum antibody was detected by neutralisation and immunofluorescence tests.


Turnover of ribosomal proteins in regenerating rat liver after partial hepatectomy.
The rates of synthesis and degradation of ribosomal proteins, prelabelled with [14C]bicarbonate, were determined as an index of the rate of ribosome turnover in regenerating rat liver. The half-life of ribosomes is about 178 and 75 hr in regenerating and normal liver, respectively. The comparison of turnover rates of ribosomal proteins with the corrected values of rRNA, based on re-utilization of nucleotides, suggests that ribosomes are metabolized as a unit in vivo. There is at least 70% overestimation for ribosome half-life when orotate-labelled RNA is used for turnover determinations. The absolute rate of synthesis is estimated as 3925 and 1081 ribosomes/min per cell in 24 hr regenerating and normal rat liver, respectively.


Lower Extremity Burns, Complications, and Outcome.
We have encountered many burn cases with lower extremity burn with adverse outcome. The study was a retrospective cohort study in 2 years, mean (SD) of follow up was 12(7) months. All demographic data, cause burn, time, total burn surface area (TBSA), presence lower extremity burn and its burn surface area (BSA), foot burn, delay in treatment, smoking, infection, morbidity, co-morbid diseases, length of stay (LOS), amputation, mortality, and outcome were gathered from patients' files. Statistical analysis was done with SPSS 21software. We had 14,215 burn patients, of them 995 were admitted according to criteria of ABA. Six hundred and ten (61.3%) were male and 358 (37%) female. Male to female ratio was 1.58:1. The mean age ± SD was 33.64 ±23.45. Mean (SD) of lower extremity BSA was 12.09 ± 9.18%. The patients who had 10 to 19% burn, had 3 times more risk of mortality than patients with 0 to 9% burn (P < .018). And those with 20 to 29% burn had 35 times more risk of mortality comparing to patients with 0 to 9% burn. The difference was significant too. (P < .000). Delay in treatment, presence of co-morbid diseases and diabetes would not do any increase in mortality. The sex, weight, cause of burn, diabetes, and delay in treatment have not any influence on the death risk. But age and lower extremity BSA have influence on the risk of death. According to statistical study: with every 1-year increase in age, death rate increased by 4% (P < .0001). With every 1% increase in lower extremity BSA, death rate increase by 9% (P < .0005) and with every 1 day increase in LOS, the death rate increase by 4%. Statistical study shows lower extremity burn, TBSA, age, and LOS have great influence on the outcome of these patients. Sex, weight, cause of burn, and delay in treatment have not affected the risk of mortality.


Is colonoscopic screening necessary for patients with gastric adenoma or cancer?
Since colorectal adenoma or cancer is commonly associated with gastric adenoma or cancer, early colorectal adenoma detection can affect the survival of gastric adenoma or cancer patients. The purpose here was to investigate the colorectal adenoma or cancer prevalence and evaluate the necessity for screening colonoscopy in gastric adenoma or cancer patients. From September 2005 through August 2010, 857 patients younger than 70 years who had gastric adenoma or cancer were enrolled. Healthy age- and sex-matched controls were selected from the general screening population. The prevalence and risk of colorectal adenoma or cancer were compared between the participants and the controls. Data from 416 patients in the gastric neoplasm group (123 with gastric adenoma and 293 with gastric cancer) and 416 healthy control group participants were included in the statistical analysis. The presence of gastric adenoma or cancer was an independent risk factor for colorectal neoplasm (OR = 1.348, 95 % CI = 1.001-1.815). Patients with diffuse type gastric cancer had a lower prevalence of colorectal adenoma or cancer than those with gastric adenoma or intestinal type cancer. In gastric cancer patients younger than 50 years, intestinal type histology was significantly associated with colorectal adenoma or cancer (OR = 3.838, 95 % CI = 1.077-13.677). The colorectal adenoma or cancer risk was significantly increased in patients with gastric adenoma or cancer. Therefore, screening colonoscopy should be considered for gastric adenoma or cancer patients including young patients, in the case of intestinal type gastric cancer.


Advantages of determining the fertile window with the individualised Natural Cycles algorithm over calendar-based methods.
Purpose: This study aims to compare the accuracy of fertile window identification with the contraceptive app Natural Cycles against the Rhythm Method and Standard Days Method (SDM).Materials and methods: Menstruation dates, basal body temperature (BBT), and luteinising hormone (LH) test results were collected anonymously from Natural Cycles app users. The fraction of green days (GDs) and wrong green days (WGDs) allocated by the various algorithms was determined over 12 cycles. For comparison of Natural Cycles and the Rhythm Method, 26,626 cycles were analysed.Results: Natural Cycles' algorithms allocated 59% GDs (LH, BBT) in cycle 12, while the fraction of WGDs averaged 0.08%. The Rhythm Method requires monitoring of six cycles, resulting in no GDs or WGDs in cycle 1-6. In cycle 7, 49% GDs and 0.26% WGDs were allocated. GDs and WGDs decreased to 43% and 0.08% in cycle 12. The probabilities of WGDs on the day before ovulation with Natural Cycles were 0.31% (BBT) and 0% (LH, BBT), and 0.80% with the Rhythm Method. The probability of WGDs on the day before ovulation was 6.90% with the SDM.Conclusions: This study highlights that individualised algorithms are advantageous for accurate determination of the fertile window and that static algorithms are more likely to fail during the most fertile days.


Should we favour the use of 5 × 5 preoperative radiation in rectal cancer.
The management of patients with "locally advanced rectal cancer" (LARC) is evolving from the original aim of reducing local recurrence. Current practice recognises the importance of surgical technique, high-quality preoperative imaging, and integration of neoadjuvant systemic chemotherapy. Contemporary protocols focus on improving survival and avoiding radical surgery with organ preservation strategies. Both short course preoperative radiotherapy (SCPRT) with immediate surgery and long-course chemoradiation (LCCRT) are standard neoadjuvant strategies, both demonstrating similar efficacy in preventing local recurrence, distant metastases and improving disease-free survival (DFS). SCPRT is highly cost-effective with high compliance rates, hence is gaining traction in Europe and East Asia, partly because of inherent flexibility in timing and the ability to add neoadjuvant systemic chemotherapy as there is a delay to surgery. SCPRT is currently not being exploited to its full extent - particularly in the USA where uptake is approximately 1% of neoadjuvant treatments for rectal cancer. We analyse the use of induction, concurrent and consolidation chemotherapy with SCPRT in a total neoadjuvant therapy (TNT) approach.


UV laser induced RNA-protein crosslinks and RNA chain breaks in tobacco mosaic virus RNA in situ.
The efficiency of RNA-protein crosslink and RNA chain break formation under nanosecond or picosecond UV-laser pulse irradiation of tobacco mosaic virus was determined. It was found that on high-intensity UV-laser irradiation the quantum yields of both reactions increase considerably as compared to the usual (low-intensity) UV-irradiation. The RNA-protein crosslink quantum yield was found to be 1.8 x 10(-5) and 1.2 x 10(-4) and that of RNA chain breaks 1.7 x 10(-4) and 8.9 x 10(-4) for nanosecond and picosecond irradiation, respectively.


Full-convolution Siamese network algorithm under deep learning used in tracking of facial video image in newborns.
This study was carried out with the aim of exploring the full-convolution Siamese network (SiamFC) in the application of neonatal facial video image tracking, achieving accurate recognition of neonatal pain and helping doctors evaluate neonatal emotions in an automatic manner. The current technology shows low accuracy on facial image recognition of newborns, so the SiamFC algorithm under the deep learning was optimized in this study. Besides, a newborn facial video image tracking model (FVIT model) was constructed based on the SiamFC algorithm in combination with the attention mechanism with face tracking algorithm, and the facial features of newborns were tracked and recognized. In addition, a newborn face database was constructed based on the adult face database to evaluate performance of the FVIT model. It was found that the accuracy of the improved algorithm is 0.889, higher by 0.036 in contrast to other models; the area under the curve (AUC) of success rate reaches 0.748, higher by 0.075 compared with other algorithms. What's more, the improved algorithm shows good performance in tracking the facial occlusion, facial expression changes, and scale conversion of newborns. Therefore, the improved algorithm shows higher accuracy and success rate and has good effect in capturing and tracking the facial images of newborns, thereby providing an experimental basis for facial recognition and pain assessment of newborns in the later stage.


Physical and perceptual-cognitive demands of top-class refereeing in association football.
The aim of this study was to examine the physical and perceptual-cognitive demands imposed on UEFA top-class referees and assistant referees during the final round of the Euro 2000 Championship. To investigate the physical workload, the heart rates during matches were monitored by short-range radio telemetry and translated to different workloads expressed as a percentage of maximal heart rate. For measurement of the perceptual-cognitive workload, video-recordings of games were used to obtain the average number of observable decisions taken by a referee. On average, referees and assistant referees performed the matches at 85 +/- 5% and 77 +/- 7% of their maximal heart rate, respectively. Over the 31 games, the mean number of observable decisions was 137 (range 104-162), 64% of which were based on communication with the assistant referees and/or the fourth official. To optimize the physical preparation of top-class match officials, the results of this study support the application of intensive and intermittent training sessions, which should place priority on high-intensity aerobic stimuli. In addition, video training is discussed as an additional method for improving match officials' decision making.


Creutzfeldt-Jakob disease via dural and corneal transplants.
A review of all published cases of iatrogenic Creutzfeldt-Jakob disease (CJD) via dural (N=71) and corneal (N=4) transplants is given. All but three of the dural cases were obviously due to a commercial product recalled in 1996. Two of the corneal grafts were taken from patients who had died of sporadic CJD. These cases differed from CJD due to human growth hormone injections and the new variant. Instead. they were akin to sporadic cases, but memory loss, disorders of higher cerebral functions and extrapyramidal signs were fewer, while cerebellar abnormalities were more frequent. Progressive dysarthria and gait disorder/gait ataxia were prominent signs during the early stages, myocloni the most salient feature later. A nonperiodic EEG did not contradict the diagnosis. Using current diagnostic criteria the disease was underdiagnosed ante mortem. Utmost care is needed in selecting, harvesting and handling dural and corneal grafts to avoid inadvertent transmission of CJD.


Proteomics to Understand the Degenerative Matter.
No matter what we do, eat or practice - sooner or later we all will start loosing our abilities to control our bodily functions, maintain muscle control and innervations. Most of us will grow old and degrade by natural causes, while some of us unfortunately will be affected by fast or slow progressive diseases or even have accidents with traumas that will initiate dramatic degenerative effects. We have recently demonstrated that a shotgun proteomic approach coupled with relative quantitative dimethyl labeling (DML) method can analyze the global changes in the human brain and skeletal muscle proteome. Very limited amount of material (biopsy) is needed for comparison. The underlying objective of our studies are to identify potential protein biomarkers related to the development of degeneration but also to be able to get in detail structural characteristics of protein modifications that are initiated by disease. These proteins are involved in several biological processes including fundamental brain function, muscle development and contraction, metabolic process, enzyme activity, glycolysis, regulation of apoptosis and transport activity. We have identified a number of different factors behind this phenomenon that also reveals new knowledge about the natural aging.


Improved thermostability, acid tolerance as well as catalytic efficiency of Streptomyces rameus L2001 GH11 xylanase by N-terminal replacement.
The N-terminal of xylanase from 11 family of glycoside hydrolases (GH11 xylanase) has an important effect on its thermostability and catalytic properties. Previous studies have unearthed five important residues located in the N-terminal and successfully improved the thermostability of several GH11 xylanases using amino acid substitutions. In the present study, we applied this tactic to construct a mutant of XynA from Streptomyces rameus L2001, XynAR, and studied its biochemical, catalytic and hydrolytic properties. The results showed that thermostability, acid tolerance as well as catalytic efficiency of XynAR significantly improved compared to those of XynA, while the hydrolytic characteristics changed. Computer simulation analysis showed that this tactic created new hydrogen bonds and electrostatic interactions in the N-terminal, resulting in decrease in the flexibility of N-terminal and surface electrostatic potential as well as a change in the profile of hydrogen bonds between the subsites and substrate in the cleft region of xylanase. This study showed that amino acid substitutions at the key sites of the N-terminal of GH11 xylanase can improve its thermostability and catalytic properties.


Simultaneous liver steatosis, fibrosis and iron deposition quantification with mDixon quant based on radiomics analysis in a rabbit model.
To evaluate the feasibility of simultaneous quantification of liver fibrosis, liver steatosis and abnormal iron deposition using mDixon Quant based on radiomics analysis, and to eliminate the interference among different histopathologic features. One hundred and twenty rabbits that were administered CCl4 for 4-16 weeks and a cholesterol rich diet for the initial 4 weeks in the experimental group and 20 rabbits in the control group were examined using mDixon. Radiomics features of the whole liver were extracted from PDFF and R2* and radiomics models for discriminating steatosis: S0-S1 vs. S2-S4, fibrosis: F0-F2 vs. F3-F4 and iron deposition: normal vs. abnormal were constructed respectively and evaluated using receiver operating characteristic (ROC) curves with the histopathological results as reference standard. Combined corrected models merging the radscore and the other two histopathologic features were evaluated using multiple logistic regression analyses and compared with radiomics models. The area under the ROC curve (AUC) of the radiomics model with PDFF features was 0.886 and 0.843 in the training and the test set, respectively, for the diagnosis of liver steatosis grade S0-1 and S2-S4. The radiomics model based on R2* features were 0.815 and 0.801 for distinguishing F0-F2 and F3-F4 and 0.831 and 0.738 for discriminating abnormal iron deposition in the training and test set, respectively. The corrected model for liver steatosis and fibrosis (0.944 and 0.912 in the test set) outperformed the radiomics models by eliminating the interference of histopathologic features(P < 0.05), but had comparable diagnostic performance for abnormal iron deposition(P > 0.05). It is feasible for mDixon to simultaneously quantify whole liver steatosis, fibrosis and iron deposition based on radiomics analysis. It is valuable to minimize the interference of different pathological features for the assessment of liver steatosis and fibrosis.


Depressive symptoms, social support, and health-related quality of life: A community-based study in Shanghai, China.
Depressive symptoms erode both physical and mental aspects of health-related quality of life (HRQoL). Social support (SS) may improve HRQoL through its direct effects or buffering effects. The association among depressive symptoms, SS, and HRQoL has been studied in specific groups, but research in the general adult population remains limited. This study examined the association among depressive symptoms, SS, and HRQoL, including exploring whether SS (including its three dimensions: subjective SS, objective SS and support utilization) mediated or moderated the relationship between depressive symptoms and HRQoL among community-based adults. We conducted a cross-sectional survey in six communities in Shanghai, China, and 1642 adult participants with complete information on depressive symptoms and/or SS, and HRQoL were included. Linear regression analysis was used to investigate the association among depressive symptoms, SS, and HRQoL. In addition, we explored the mediating and moderating role of SS in the relationship between depressive symptoms and HRQoL. More depressive symptoms were associated with lower physical HRQoL (B = -0.64, p < .001) and lower mental HRQoL (B = -0.83, p < .001). SS (B = 0.07, p = .02), specifically subjective SS (B = 0.09, p = .03), was positively related to mental HRQoL. After adjusting for covariates, we found no evidence for a mediating role of SS in the relationship between depressive symptoms and HRQoL, while SS (subjective SS and objective SS) moderated the association between depressive symptoms and mental HRQoL. Due to the low voluntary participation rate of employees, participants represented approximately 50% of the individuals approached, thus limiting the generalizability of our findings. Data collected through self-report scales could lead to information bias. SS does not appear to underlie the relationship between depressive symptoms and HRQoL. However, interventions to increase SS (in particular, subjective SS and objective SS) should be studied to determine whether they may be beneficial in alleviating the adverse impact of depressive symptoms on mental HRQoL.


Publisher Correction: Oncogenic hijacking of a developmental transcription factor evokes vulnerability toward oxidative stress in Ewing sarcoma.
A Correction to this paper has been published: https://doi.org/10.1038/s41467-020-20017-2.


Operationalizing a Structural Vulnerability Profile for forensic anthropology: Skeletal and dental biomarkers of embodied inequity.
Human societies create and maintain structures in which individuals and groups experience varying degrees of inequity and suffering that may be skeletally and dentally embodied. It is necessary to foreground these social and structural impacts for forensic anthropologists to eschew biologically deterministic interpretations of human variation and overly individualistic interpretations of health and disease. We thus propose a 'Structural Vulnerability Profile' (SVP), akin to the Structural Vulnerability Assessment Tool of medical anthropology [1], to be considered along with the traditional 'biological' profile estimated by forensic anthropologists. Assembling an SVP would involve examining and assessing skeletal/dental biomarkers indicative of embodied social inequity-the lived experiences of social marginalization that can get 'under the skin' to leave hard-tissue traces. Shifting our emphasis from presumably hereditary variation to focus on embodied social marginalization, the SVP will allow forensic anthropologists to sensitively reconstruct the lived experiences of the people we examine.


Astrocytic Cx43 and Cx30 differentially modulate adult neurogenesis in mice.
In addition to their well known function in astrocyte coupling, gap junction forming connexins are also important for cell proliferation, migration and differentiation during brain development. The aim of this study was to determine whether loss of the main astrocytic connexins, connexin 43 (Cx43) or connexin 30 (Cx30), influences various stages of adult hippocampal neurogenesis. To that end, mice with a conditional Cx43 deletion in astrocytes and mice with a conventional knockout of Cx30 were used. We assessed cell proliferation based on Ki67-immunoreactive cell number and cell survival based on BrdU-immunoreactive cell number in the subgranular zone (SGZ) and the granular cell layer (GCL) of the dentate gyrus. The neuronal phenotype of surviving cells was analyzed following immunofluorescent co-localization of BrdU-positive cells with the neuronal markers doublecortin (DCX) and neuronal nuclear antigen (NeuN). Ablation of Cx43 in astrocytes significantly diminished proliferation and reduced the overall survival of newborn cells. In contrast, knockout of Cx30 showed a tendency towards increased proliferation and significantly enhanced the overall survival of newborn cells. The differentiation of surviving cells into neurons is unaffected following Cx43 or Cx30 knockout. Our data reveal that Cx43 promotes the survival of newborn neurons in the adult mouse hippocampus whereas Cx30 restricts their survival.


Cardiovascular autonomic neuropathy and incident diabetic kidney disease in patients with type 2 diabetes.
We investigated the association between cardiovascular autonomic neuropathy (CAN) and incident diabetic kidney disease (DKD). This retrospective longitudinal study included 2,033 patients with type 2 diabetes (mean age 57.2 years, 57.4% male, and median diabetes duration 8.0 years), free of renal dysfunction or cardiovascular disease at initiation. Cardiovascular autonomic reflex tests were performed once at baseline, and CAN was defined as ≥ 2 abnormal parasympathetic test results. Urine ACR and eGFR were concurrently measured at baseline and every 3-6 months thereafter. Incident DKD was defined as the development of ACR ≥ 30 mg/g at two or more follow-up examinations or eGFR < 60 ml/min/1.73 m2 with ≥ 25% decrease from baseline. During a median follow-up of 2.9 years (1.1 - 4.8), 290 (14.3%) patients developed DKD, comprising 79.7% (N = 231) cases of new-onset albuminuria alone, 14.5% (N = 42) cases of eGFR decline alone, and 5.8% (N = 17) cases of both. Compared to those without CAN, patients with CAN had a significantly higher risk of incident DKD in a multivariable Cox regression model (HR 1.56, 95% CI 1.15 - 2.12; P = 0.005). CAN is may be a useful marker for long-term complications including DKD in patients with type 2 diabetes. Monitoring of CAN helps to identify high risk patients of future renal impairment.


Preparation, property of the complex of carboxymethyl chitosan grafted copolymer with iodine and application of it in cervical antibacterial biomembrane.
Cervical erosion is one of the common diseases of women. The loop electrosurgical excisional procedure (LEEP) has been used widely in the treatment of the cervical diseases. However, there are no effective wound dressings for the postoperative care to protect the wound area from further infection, leading to increased secretion and longer healing time. Iodine is a widely used inorganic antibacterial agent with many advantages. However, the carrier for stable iodine complex antibacterial agents is lack. In the present study, a novel iodine carrier, Carboxymethyl chitosan-g-(poly(sodium acrylate)-co-polyvinylpyrrolidone) (CMCTS-g-(PAANa-co-PVP), was prepared by graft copolymerization of sodium acrylate (AANa) and N-vinylpyrrolidone (NVP) to a carboxymethyl chitosan (CMCTS) skeleton. The obtained structure could combine prominent property of poly(sodium acrylate) (PAANa) anionic polyelectrolyte segment and good complex property of polyvinylpyrrolidone (PVP) segment to iodine. The bioactivity of CMCTS could also be kept. The properties of the complex, CMCTS-g-(PAANa-co-PVP)-I2, were studied. The in vitro experiment shows that it has broad-spectrum bactericidal effects to virus, fungus, gram-positive bacteria and gram-negative bacteria. A CMCTS-g-(PAANa-co-PVP)-I2 complex contained cervical antibacterial biomembrane (CABM) was prepared. The iodine release from the CABM is pH-dependent. The clinic trial results indicate that CABM has better treatment effectiveness than the conventional treatment in the postoperative care of the LEEP operation.


Recommendations made by patients, caregivers, providers, and decision-makers to improve transitions in care for older adults with hip fracture: a qualitative study in Ontario, Canada.
Older adults frequently experience fall-related injuries, including hip fractures. Following a hip fracture, patients receive care across a number of settings and from multiple different providers. Transitions between providers and across settings have been noted as a vulnerable time, with potentially negative impacts. Currently, there is limited research on how to improve experiences with transitions in care following a hip fracture for older adults from the perspectives of those with lived experienced. The purpose of this study was to explore service recommendations made by patients, caregivers, healthcare providers, and decision-makers for improving transitions in care for older adults with hip fracture. This descriptive qualitative study was part of a larger longitudinal qualitative multiple case study. Participants included older adults with hip fracture, caregivers supporting an individual with hip fracture, healthcare providers, and decision-makers. In-depth, semi-structured interviews were conducted with all participants, with patients and caregivers having the opportunity to participate in follow-up interviews as they transitioned out of hospital. All interviews were audio-recorded, transcribed verbatim, and analyzed thematically. A total of 47 participants took part in 65 interviews. We identified three main categories of recommendations: (1) hospital-based recommendations; (2) community-based recommendations; and (3) cross-sectoral based recommendations. Hospital-based recommendations focused on treating patients and families with respect, improving the consistency, frequency, and comprehensiveness of communication between hospital providers and between providers and families, and increasing staffing levels. Community-based recommendations included the early identification of at-risk individuals and providing preventative and educational programs. Cross-sectoral based recommendations were grounded in enhanced system navigation through communication and care navigators, particularly within primary and community care settings. Our findings highlighted the central role primary care can play in providing targeted, integrated services for older adults with hip fracture. The recommendations outlined have the potential to improve experiences with care transitions for older adults with hip fracture, and thus, addressing and acting on them should be a priority.


Role of Transglutaminase 2 in Migration of Tumor Cells and How Mouse Models Fit.
A search for the "magic bullet", a molecule, the targeting abilities of which could stop the migration of tumor cells, is currently underway, but remains in the early stages. There are still many unknowns regarding the cell migration. The main approach is the employment of mouse models, that are sources of valuable information, but still cannot answer all of the questions. One of the molecules of interest is Transglutaminase 2 (TG2). It is a well-described molecule involved in numerous pathways and elevated in metastatic tumors. The question remains whether mice and humans can give the same answer considering TG2.


131I effective half-life (Teff) for patients with thyroid cancer.
Nuclear medicine procedures that use I activity represent significant sources of potential absorbed dose to medical staff, volunteers, and the general public. The potential exposures are due principally from exposures to excreted and retained activities in the patients' bodies. In general, exposure rate decreases in a simple exponential manner. The average effective half-life found for all patients in the study reported here is 11.41 +/- 0.02 h; this information may be used in guidelines on the management of patients in thyroid cancer therapy and for general radioprotection practice.


Comparison of Pathological Radicality between Open and Laparoscopic Pancreaticoduodenectomy in a Tertiary Centre.
Laparoscopic pancreaticoduodenectomy (LPD) remained a formidable challenge owing to retroperitoneal location, difficult dissection near great vessels and critical intracorporeal anastomoses. Recent reviews of literature have established the feasibility and comparable short term outcomes of laparoscopic pancreaticoduodenectomy (LPD) with that of open pancreaticoduodenectomy (OPD). This study was undertaken to compare the pathological radicality of LPD with OPD. A prospective database of all patients who underwent standard pancreaticoduodenectomy from Mar 2006 to Feb 2011 was taken up for this study. 45 patients who underwent LPD and 118 patients who underwent OPD for periampullary and pancreatic head malignancy were taken up for analysis. The study groups were comparable in terms of age of presentation, ASA grades, comorbidity, type of surgery and BMI. There was no statistically significant difference with regard to tumor size, lymph node yield, node positivity rates, R1 rates and margin lengths. The pathological radicality of laparoscopic pancreaticoduodenectomy is comparable with that of open approach when performed by experienced minimal-access surgeons. Standardized protocols for evaluation of the resection margins should be mandatory in studies reporting outcomes of pancreaticoduodectomy.


Neuromodulation therapy for atrial fibrillation.
Atrial fibrillation has a multifactorial pathophysiology influenced by cardiac autonomic innervation. Both sympathetic and parasympathetic influences are profibrillatory. Innovative therapies targeting the neurocardiac axis include catheter ablation or pharmacologic suppression of ganglionated plexi, renal sympathetic denervation, low-level vagal stimulation, and stellate ganglion blockade. To date, these therapies have variable efficacy. As our understanding of atrial fibrillation and the cardiac nervous system expands, our approach to therapeutic neuromodulation will continue evolving for the benefit of those with AF.


The treatment of lupus nephritis.
The literature on the treatment of lupus nephritis is scattered, much of it in rheumatological rather than nephrological journals. Whatever our ignorance of the nature and genesis of lupus nephritis, under empirical treatment the prognosis, especially for severe forms, has improved dramatically during the past 20 years. For severe lupus nephritis, the evidence that the addition of cytotoxic agents to corticosteroids improves outcome is now secure, and discussion centres mainly on which drug to use and by what route. Intravenous methylprednisolone is at least as effective as high-dose tapering oral therapy for initial treatment, and carries fewer side-effects. The role of plasma exchange in lupus remains undefined: it may have a role in the treatment of cerebral manifestations or otherwise resistant patients, but controlled trials have failed to show benefit. Future developments will probably centre around the use of specific monoclonal antibodies which target specific groups and subgroups of cells, "humanised" by the splicing of human Fc piece to rodent (fab)2, perhaps bearing toxins. To use these agents to best advantage, however, we will have to understand better than we do today the nature of the cellular defects in the immune response which underlie the lupus syndrome.


Fluorescence-based assays for microtubule architecture.
In vitro fluorescence-based assays have enabled the direct observation of single microtubule-associated proteins (MAPs) alongside the measurement of microtubule growth and shrinkage. Fluorescence-based assays have not, however, been able to address questions of "microtubule architecture." Tubulin can form diverse polymer structures in vitro. Importantly, microtubules nucleated spontaneously have different numbers of protofilaments (pfs), ranging from 11-pf to 16-pf, as well as sheet-like structures, indicating flexibility in tubulin-tubulin bonds. This structural diversity influences microtubule dynamics and the binding of MAPs to microtubules. Observation of microtubule architecture has required the imaging of microtubules by electron microscopy (EM). Because EM requires chemical fixation or freezing, it has not been possible to observe, in real time, how microtubule dynamics might influence structure and vice versa; it also remains technically challenging to directly observe some MAPs, especially small ones, by EM. It is therefore imperative to develop fluorescence-based assays that enable the direct, real-time observation of microtubule architecture alongside growth, shrinkage, and MAP binding. In this chapter, we describe our efforts to control microtubule architecture for fluorescence-based assays. We also describe how microtubule structure can be probed with the help of GFP-tagged doublecortin, a MAP that binds preferentially to 13-pf microtubules.


Mesenchymal stem cell therapy of acute thermal burns: A systematic review of the effect on inflammation and wound healing.
Mesenchymal stem cell (MSC) therapies are emerging as a promising strategy to promote tissue repair, and may extend their utility to burn care. This comprehensive review of the extant literature, evaluated all in vivo studies, to elucidate the potential protective and therapeutic effect of MSCs in acute thermal skin burns. PubMed was systematically searched, according to PRISMA guidelines, and all relevant preclinical and clinical studies were included according to pre-specified eligibility criteria. Forty-two studies were included in a qualitative synthesis, of which three were human and 39 were animal studies. The preclinical studies showed that MSCs can significantly reduce inflammation, burn wound progression and accelerate healing rate of acute burns. The underlying mechanisms are complex and not fully understood but paracrine modulators, such as immunomodulatory, antioxidative and trophic factors, seem to play important roles. Allogeneic MSC therapy has proved feasible in humans, and could allow for prompt treatment of acute burns in a clinical setting. MSC therapy show positive results, regarding improved burn wound healing and immunologic response. However, most findings are based on small animal studies. Randomized clinical trials are warranted to investigate the regenerative effects in human burns before translating the findings into clinical practice.