Fast method for brain image segmentation: application to proton magnetic resonance spectroscopic imaging.
The interpretation of brain metabolite concentrations measured by quantitative proton magnetic resonance spectroscopic imaging (MRSI) is assisted by knowledge of the percentage of gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) within each MRSI voxel. Usually, this information is determined from T(1)-weighted magnetic resonance images (MRI) that have a much higher spatial resolution than the MRSI data. While this approach works well, it is time-consuming. In this article, a rapid data acquisition and analysis procedure for image segmentation is described, which is based on collection of several, thick slice, fast spin echo images (FSE) of different contrast. Tissue segmentation is performed with linear "Eigenimage" filtering and normalization. The method was compared to standard segmentation techniques using high-resolution 3D T(1)-weighted MRI in five subjects. Excellent correlation between the two techniques was obtained, with voxel-wise regression analysis giving GM: R2 = 0.893 +/- 0.098, WM: R2 = 0.892 +/- 0.089, ln(CSF): R2 = 0.831 +/- 0.082). Test-retest analysis in one individual yielded an excellent agreement of measurements with R2 higher than 0.926 in all three tissue classes. Application of FSE/EI segmentation to a sample proton MRSI dataset yielded results similar to prior publications. It is concluded that FSE imaging in conjunction with Eigenimage analysis is a rapid and reliable way of segmenting brain tissue for application to proton MRSI.


Genomic expression patterns distinguish long-term from short-term glioblastoma survivors: a preliminary feasibility study.
We used microarray analysis to investigate associations between genotypic expression profiles and survival phenotypes in patients with primary glioblastoma (GBM). Tumor samples from 7 long-term glioblastoma survivors (>24 months) and 13 short-term survivors (<9 months) were analyzed to detect differential patterns of gene expression between these groups and to identify genotypic subclasses of glioblastomas that correlate with survival phenotypes. Five unsupervised and three supervised clustering algorithms consistently and accurately grouped the tumors into genotypic subgroups corresponding to the two clinical survival phenotypes. Three unique prospective mathematical classification algorithms were subsequently trained to use expression data to stratify unknown glioblastomas between survival groups and performed this task with 100% accuracy in validation studies. A set of 1478 genes with significant differential expression (p<0.01) between long-term and short-term survivors was identified, and additional mathematical filtering was used to isolate a 43-gene "fingerprint" that distinguished survival phenotypes. Differential regulation of a subset of these genes was confirmed using RT-PCR. Gene ontology analysis of the fingerprint demonstrated pathophysiologic functions for the gene products that are consistent with current models of tumor biology, suggesting that differential expression of these genes may contribute etiologically to the observed differences in survival. These results demonstrate that unique expression profiles characterize genotypic subsets of primary GBMs associated with differential survival phenotypes, and these profiles can be used in a prospective fashion to assign unknown tumors to survival groups. Future efforts will focus on building more robust classifiers and identifying additional subclasses of gliomas with phenotypic significance.


Role of a new age-adjusted D-dimer cutoff value for preoperative deep venous thrombosis exclusion in elderly patients with hip fractures.
This study aimed to describe the characteristics of plasma D-dimer level with increasing age and establish a new age-adjusted D-dimer cutoff value for excluding preoperative lower limb deep vein thrombosis (DVT) in elderly patients with hip fractures. This was a retrospective study of elderly patients who presented with acute hip fracture in our institution between June 2016 and June 2019. All patients underwent D-dimer test and duplex ultrasound. Patients were divided into six 5-year-apart age groups. The optimal cutoff value for each group was calculated by using receiver operating characteristic (ROC) curves, whereby the new age-adjusted D-dimer cutoff value was determined. The sensitivity, specificity, positive predictive values (PPV) and negative predictive values (NPV) were calculated and compared when different D-dimer cutoff values were applied, i.e., conventional 0.5 mg/L, previously well-established age-adjusted cutoff value (age × 0.01 mg/L) and the new age-adjusted D-dimer cutoff value herein. There were 2759 patients included, 887 males and 1872 females, with an average age of 78 years. In total, 280 patients were diagnosed with preoperative DVT. The optimal cutoff values for the six age groups were 0.715 mg/L, 1.17 mg/L, 1.62 mg/L, 1.665 mg/L, 1.69 mg/L and 1.985 mg/L, respectively, and the calculated age-adjusted coefficient was 0.02 mg/L. With this new coefficient applied, the specificity was 61%, clearly higher than those for conventional threshold (0.5 mg/L, 37%) or previously established age-adjusted D-dimer threshold (age × 0.01 mg/L, 22%). In contrast, the sensitivity was lower than that (59% vs 85% or 77%) when D-dimer threshold of 0.5 mg/L or age-adjusted cutoff value (age × 0.01 mg/L) was used. The other indexes as PPV (15%, 11% and 12%) and NPV (93%, 93% and 94%) were comparable when three different D-dimer thresholds were applied. We developed a new age-adjusted D-dimer cutoff value (age × 0.02 mg/L) for a specified high-risk population of patients aged 65 years or older with hip fractures, and demonstrated the improved utility of the D-dimer test for exclusion of DVT. This formula can be considered for use in elderly hip fracture patients who meet the applicable standards as preoperative DVT screening, after its validity is confirmed by more well-evidenced studies.


Single nucleotide polymorphisms (rs3736228 and rs4988321) in low-density lipoprotein receptor-related protein-5 gene with predisposition to rheumatoid arthritis.
LRP5 (Lipoprotein Receptor 5) is one of the representatives of the low-density lipoprotein receptors family that play a crucial role in the process of bone homeostasis and bone remodeling. The role of LRP5 single nucleotide polymorphisms (SNPs) rs3736228 and rs4988321 has been associated with the susceptibility to osteoporosis and bone fracture. The frequency of mentioned LRP5 SNPs is unknown among RA (Rheumatoid Arthritis) patients. The case-control study was designed to determine the association of targeted SNPs among RA patients. Patients were selected by ACR/EULAR 2010 criteria. After ethical approval blood samples of patients and healthy individuals were collected. DNA was extracted from the whole blood followed by amplification of the targeted region by T-ARMS PCR (Tetra-primer Amplification Refractory Mutation System) obtained product was observed on agarose gel electrophoresis. The data were analyzed by statistical and bioinformatic tools. It was observed that the SNPs rs3736228 and rs4988321 showed significant association with the risk of RA [χ2 = 44, p =< 0.001, O.R 95 % CI = 2.495, (1.865 ∼ 3.337), p =< 0.001] and [χ2 = 85, p =< 0.001, O.R 95 % CI = 2.05, (1.571 ∼ 2.69), p =< 0.001] respectively. Haplotypes AT, GC, and GT were found to be significantly associated with the risk of RA. Furthermore, both SNPs were in 40 % LD (Linkage Disequilibrium). The study revealed that SNPs rs3736228 and rs4988321 were significantly associated with the increased susceptibility to RA. The study serves as the baseline data considering targeted SNPs and their association with the progression of the disease. The study might be utilized for the development of potential biomarker for diagnostic purposes and in the precision medicine approach.


The effect of the fourth-generation fluoroquinolones on corneal reepithelialization after penetrating keratoplasty.
To compare the effects of topical moxifloxacin and gatifloxacin on corneal reepithelialization after penetrating keratoplasty. In this single-center, open-label, prospective study, 46 consecutive patients requiring penetrating keratoplasty were alternately assigned to receive either postoperative moxifloxacin 0.5% ophthalmic solution (n = 23; Vigamox) or gatifloxacin 0.3% ophthalmic solution (n = 23; Zymar). The primary outcome measure was the area of the epithelial defect measured by slit-lamp evaluation during the postoperative period. The mean area of the epithelial defect was similar in both treatment groups at baseline (P = 0.104), but it was significantly larger in the moxifloxacin group than in the gatifloxacin group at day 4 (23.9 mm2 versus 10.6 mm2, respectively; P < .001) and day 7 (3.8 mm2 versus 0.85 mm2, respectively; P = 0.03). At every follow-up visit after day 4, there were more eyes with complete reepithelialization of the corneal graft in the gatifloxacin group than in the moxifloxacin group (statistically significant at days 7 and 14). The results of this preliminary study suggest that the postoperative use of gatifloxacin in corneal transplant patients may allow the early stages of corneal graft reepithelialization to proceed more quickly than does treatment with moxifloxacin. These findings suggest that a larger, masked, randomized clinical study in a more homogeneous patient population is warranted to further investigate the relative effects of moxifloxacin and gatifloxacin on postoperative corneal wound healing.


Lentiviral Gene Transfer Corrects Immune Abnormalities in XIAP Deficiency.
X-linked inhibitor of apoptosis protein (XIAP) deficiency is a severe immunodeficiency with clinical features including hemophagocytic lymphohistiocytosis (HLH) and inflammatory bowel disease (IBD) due to defective NOD2 responses. Management includes immunomodulatory therapies and hematopoietic stem cell transplant (HSCT). However, this cohort is particularly susceptible to the chemotherapeutic regimens and acutely affected by graft-vs-host disease (GvHD), driving poor long-term survival in transplanted patients. Autologous HSC gene therapy could offer an alternative treatment option and would abrogate the risks of alloreactivity. Hematopoietic progenitor (Lin-ve) cells from XIAPy/- mice were transduced with a lentiviral vector encoding human XIAP cDNA before transplantation into irradiated XIAP y/- recipients. After 12 weeks animals were challenged with the dectin-1 ligand curdlan and recovery of innate immune function was evaluated though analysis of inflammatory cytokines, body weight, and splenomegaly. XIAP patient-derived CD14+ monocytes were transduced with the same vector and functional recovery was demonstrated using in vitro L18-MDP/NOD2 assays. In treated XIAPy/- mice, ~40% engraftment of gene-corrected Lin-ve cells led to significant recovery of weight loss, splenomegaly, and inflammatory cytokine responses to curdlan, comparable to wild-type mice. Serum IL-6, IL-10, MCP-1, and TNF were significantly reduced 2-h post-curdlan administration in non-corrected XIAPy/- mice compared to wild-type and gene-corrected animals. Appropriate reduction of inflammatory responses was observed in gene-corrected mice, whereas non-corrected mice developed an inflammatory profile 9 days post-curdlan challenge. In gene-corrected patient CD14+ monocytes, TNF responses were restored following NOD2 activation with L18-MDP. Gene correction of HSCs recovers XIAP-dependent immune defects and could offer a treatment option for patients with XIAP deficiency.


Double circular stapler technique for bowel resection in rectosigmoid endometriosis.
To reduce bladder function impairment and avert the serious complications of anastomotic leakage after segmental rectosigmoidectomy and to minimize the persistence of endometriotic lesions associated with discoid resection, we used the double circular stapling (DCS) technique. This technique enables excision of bowel endometriosis nodules larger than those that can be removed with the single-load technique of the circular stapler. Of 120 patients who underwent surgery to treat bowel endometriosis, intestinal shaving was performed in 24, discoid resection with single circular stapling in 40, and rectosigmoidectomy in 55. Eleven patients (9.2%) underwent the DCS technique. In the DCS group, the size of the rectosigmoid lesion ranged from 2.2 cm to 4.2 cm. Median operative time for the DCS technique was 100 minutes, compared with 150 minutes for rectosigmoidectomy (p = .04). Only 1 of 11 patients (9%) had urinary retention, compared with postoperative urinary retention in 14 of 55 patients (25%) who had undergone rectosigmoidectomy (difference not significant). Only 1 patient, with a 4.2-cm nodule, had a positive margin in the specimen obtained at the second stapling. DCS is a promising technique and may avert rectosigmoidectomy in selected patients.


Psychosocial work conditions as predictors of quality of life at the beginning of older age.
The purpose of this study was to assess the impact of psychosocial nature of previous work activity on different dimensions of subjective health and life satisfaction at the beginning of older age. The cross-sectional study was performed on a simple random sample of a 65-year-old cohort of community-dwelling citizens of Kraków. All of the 733 participants (412 women, 321 men) were interviewed face to face in their households. Two separate models have been developed to analyze indicators of health-related quality of life: the first model assessed the influence of divergences between psychological job demands and perceived job control and rewards (adjusted to job physical demands), the other explored the impact of divergences between job effort on job control and rewards (adjusted to psychological demands). High physical job demands combined with low job control diminished job satisfaction in women. High physical job demands/efforts combined with low control/reward decreased self-rated health scores. Contrary to expectations high psychological job demands combined with low job control diminished the risk of chronic diseases in women. High physical job demands/efforts combined with low job control/rewards increased the functional independence in both genders. Psychosocial conditions of work significantly influenced health-related quality of life at the beginning of older age and their patterns of influence differed between men and women.


Physiological properties of intradental mechanoreceptors.
A major role of tooth receptors in signaling overt or impending tissue damage (nociception) has been previously established by substantial evidence from mechanical, thermal and chemical stimulation of exposed dentin. We report evidence showing that some intradental receptors in canine teeth of the cat detect mechanical transients applied to intact enamel. This new finding suggests that dental innervation may play an important non-nociceptive role in oral function such as detecting tooth contact during mastication and swallowing.


A technique to produce a mirror-image wax pattern of an ear using rapid prototyping technology.
This article describes the use of computer-aided techniques to produce a wax pattern of a missing ear. A 3-dimensional (3-D) computer model of a conventional cast from a patient was obtained using an optical surface capture device (scanner). The 3-D computer model was inverted, using computer-aided design software. A physical thermoplastic (wax) pattern of the inverted 3-D cast was produced using a rapid prototyping (RP) machine.


Cloning and functional characterization of a new Ski homolog, Fussel-18, specifically expressed in neuronal tissues.
The Sloan Kettering Virus (Ski) family of nuclear oncoproteins represses transforming growth factor-beta (TGF-beta) signaling through inhibition of transcriptional activity of Smad proteins. Here, we report the discovery of a new functional Smad suppressing element on chromosome 18 (Fussel-18). Fussel-18 encodes for a protein of 297 amino acids sharing characteristic structural features, significant homology and similar genomic organization with the homolog Ski family members, Ski and Ski-related novel sequence (Sno). In contrast to Ski and Sno, which are ubiquitously expressed in human tissues, in situ hybridization, RT-PCR, Western blot and immunohistochemistry revealed a highly specific expression pattern for Fussel-18 in neuronal tissues, especially in the cerebellum, the spinal cord and dorsal root ganglia, during both embryogenesis and adult stage. Functionally, we determined interaction of Fussel-18 with Smad 2 and Smad 3 together with an inhibitory activity on TGF-beta signaling. Fussel-18 is the first example of a Smad-binding protein with a highly restricted expression pattern within the nervous system.


Prevalence of Adeno-Associated Virus 3 Capsid Binding and Neutralizing Antibodies in Healthy and Hemophilia B Individuals from India.
Adeno-associated virus (AAV) vector-based gene therapy offers a new treatment option for individuals with hemophilia. Pre-existing anti-AAV antibodies significantly impact the use of AAV vectors. Even relatively low titers of AAV neutralizing antibodies (NAb) from natural AAV infections against the capsid have been shown to inhibit the transduction of intravenously administered AAV in animal models and were associated with limited efficacy in human trials. This is important for determining the primary eligibility of patients for AAV vector-based gene therapy clinical trials. Current techniques to screen AAV antibodies include AAV capsid enzyme-linked immunosorbent assay (ELISA) for total antibodies and a transduction inhibition assay (TIA) for NAb. This study developed and screened total capsid binding anti-AAV3 antibodies by using ELISA and determined NAb levels by TIA using mCherry flow cytometry in healthy individuals with hemophilia B in India. One hundred and forty-three apparently healthy controls and 92 individuals with hemophilia B were screened. The prevalence of total and NAb in healthy controls was 79.7% and 65%, respectively; the prevalence of total and NAb in patients with hemophilia B for AAV3 was 92.4% and 91.3%, respectively.


Effects of COVID-19 on mortality: A 5-year population-based study in Oman.
Mortality surveillance provides a crucial method for monitoring disease activity. Coronavirus disease 2019 (COVID-19) can cause excess mortality both directly and indirectly by increasing deaths from other diseases. The aim of this study was to investigate the effects of COVID-19 on mortality in Oman. A cross-sectional retrospective analysis of mortality data from 1 January 2015 to 16 August 2020 was undertaken. Baseline mortality estimated using the Farrington flexible model and excess mortality were calculated for the pandemic period (16 March-16 August 2020) according to cause of death, place of death and age group. During the pandemic period, there was a 15% [95% confidence interval (CI) 14-17] increase in all-cause mortality from baseline. When classifying by cause, there was a 9% (95% CI 5-12) increase in deaths due to respiratory diseases, a 2% (95% CI 1-4) increase in deaths due to infectious diseases and a 9% (95% CI 8-11) increase in unclassified deaths. In terms of place of death, 12% (95% CI 11-14) of excess mortality occurred in hospitals and 7% (95% CI 5-8) occurred in homes during the pandemic period. Patients aged >60 years recorded a 15% (95% CI 13-16) increase in all-cause mortality during this period. The COVID-19 pandemic has resulted in a 15% increase in all-cause mortality in Oman, mainly as a result of deaths from COVID-19. However, unclassified deaths, deaths due to respiratory diseases and deaths due to infectious diseases have also increased, enforcing the need for a holistic approach and appropriate coordination of health services during such health crises.


Delivery of nitric oxide with a nanocarrier promotes tumour vessel normalization and potentiates anti-cancer therapies.
Abnormal tumour vasculature has a significant impact on tumour progression and response to therapy. Nitric oxide (NO) regulates angiogenesis and maintains vascular homeostasis and, thus, can be delivered to normalize tumour vasculature. However, a NO-delivery system with a prolonged half-life and a sustained release mechanism is currently lacking. Here we report the development of NanoNO, a nanoscale carrier that enables sustained NO release to efficiently deliver NO into hepatocellular carcinoma. Low-dose NanoNO normalizes tumour vessels and improves the delivery and effectiveness of chemotherapeutics and tumour necrosis factor-related, apoptosis-inducing, ligand-based therapy in both primary tumours and metastases. Furthermore, low-dose NanoNO reprogrammes the immunosuppressive tumour microenvironment toward an immunostimulatory phenotype, thereby improving the efficacy of cancer vaccine immunotherapy. Our findings demonstrate the ability of nanoscale NO delivery to efficiently reprogramme tumour vasculature and immune microenvironments to overcome resistance to cancer therapy, resulting in a therapeutic benefit.


GITR, a member of the TNF receptor superfamily, is costimulatory to mouse T lymphocyte subpopulations.
GITR (glucocorticoid-induced TNFR family related gene) is a member of the TNFR superfamily (TNFRSF) that is expressed in different cell types, including T lymphocytes. Because of a high homology in its cytoplasmic region with other known costimulatory members of the TNFRSF, we investigated whether GITR played a costimulatory role in T lymphocyte subpopulations. Our results show that the proliferation response of CD8+ and CD4+ peripheral T cell subpopulations was potentiated when a GITR costimulus was added to an anti-CD3 stimulus. Furthermore, expression of the main activation-induced receptor (IL-2Ralpha) and production of IL-2 and IFN-gamma were increased more with a GITR costimulus than with anti-CD3 alone. GITR stimulation also enhanced anti-CD3-induced ERK phosphorylation, suggesting that GITR is involved in MAPK-pathway activation. Interestingly, CD4+CD25+ regulatory T cell (Treg cell) proliferation was triggered by the GITR costimulus; Treg cell proliferation was paralleled by the loss of the anergic phenotype and suppressor activity. Nevertheless, unstimulated GITR(-/-) CD4+CD25+ and GITR(+/+) CD4+CD25+ cells were equally able to exert suppressor activity on CD4+CD25- responder cells. These results indicate a novel function for GITR as costimulatory molecule of T cell subsets.


Malakoplakia of the pancreas.
We report a case of malakoplakia arising in the pancreas of a 45-year-old woman. Clinical and histological features are described. Malakoplakia was present with chronic pancreatitis and adenocarcinoma. The aetiology of malakoplakia at this site may be due to a stromal response to carcinoma or an abnormal localised histiocytic response to infection or inflammation. This case and previous reported cases suggest that the aetiology and pathogenesis of pancreatic malakoplakia is not the same for all patients.


In vivo and in vitro studies of MUC1 regulation in sheep endometrium.
In this study, we investigated the expression of mucin 1 (MUC1) mRNA and protein in sheep endometrium at different time points during follicular and luteal phases of estrous cycle, and also determined the effect of steroid hormone treatments and interferon tau (IFNτ) on MUC1 mRNA expression in endometrial cell culture in vitro. In experiment one, 15 Welsh mountain ewes were synchronized to a common estrus and killed at precise stages of estrous cycle corresponding to (1) pre-LH peak, (2) LH peak, (3) post-LH peak, (4) early luteal, and (5) mid-luteal. Reproductive tracts were harvested and mRNA was extracted from the endometrial tissues. Parts of the uterine horns were fixed for immunohistochemistry. In experiment two, mixed populations of ovine endometrial cells (from slaughterhouse material collected at the postovulatory stage of the estrous cycle) were cultured to 70% confluence before treatment with (1) progesterone (P4, 10 ng/mL, for 48 hours), (2) estradiol (E2, 100 pg/mL, for 48 hours), or with (3) E2 priming for 12 hours (100 pg/mL) followed by P4 (10 ng/mL) for 36 hours. These were compared with: (4) IFNτ (10 ng/mL, for 48 hours), and (5) basic medium (Dulbecco Modified Eagle Medium /F12) as control. The results showed that MUC1 mRNA and protein expression in sheep endometrium were highest during the midluteal stage and very low during the post-LH period compared with the other stages (P < 0.05). MUC1 immunostaining in the luminal epithelium was apically restricted and was not significantly different across all stages of estrous cycle except at the post-LH peak where it was significantly low. In cell culture, MUC1 mRNA expression was significantly upregulated by both steroids either singly or in combination (P < 0.05), and downregulated in the presence of IFNτ. In conclusion, endometrial MUC1 expression is cyclically regulated by both E2 and P4in vivo and in vitro, and directly downregulated by IFNτ treatment in vitro.


Heart failure, atrial fibrillation and neuromuscular disorders influence mortality in left ventricular hypertrabeculation/noncompaction.
The prognosis of patients with left ventricular hypertrabeculation/noncompaction (LVHT) is controversial. The aim of the study was to assess parameters influencing mortality and to compare the mortality of LVHT patients with that of the general population of Austria. Included were patients with LVHT diagnosed echocardiographically between June 1995 and February 2011. They underwent a baseline cardiologic examination and were invited for neurological investigation. Between January and February 2011, their survival status was assessed. LVHT was diagnosed in 162 patients (46 females, aged 53 ± 16 years) with a prevalence of 0.31%/year. One hundred and sixteen patients (72%) underwent a neurological investigation which revealed specific neuromuscular disorders (NMD) in 25 and NMD of unknown etiology in 74 patients, and 17 subjects were assessed as normal. During the follow-up of 67 months, mortality was 4.8%/year and the standardized mortality ratio was 6.27, compared with the Austrian population. By multivariate analysis, predictors of mortality were heart failure (hazard ratio 3.91, 4.48 and 5.37 for the New York Heart Association class II, III and IV, respectively), atrial fibrillation (hazard ratio 3.26) and NMD (hazard ratio 1.86). Prognostic predictors in LVHT are heart failure, atrial fibrillation and NMD. Whether optimal therapy of heart failure and atrial fibrillation will improve the prognosis of LVHT patients has to be addressed by further studies.


Novel innovative computer-based test (Inno-CBT) item types for national licensing examinations for health care professionals.
An effective test mechanism to evaluate clinical knowledge and skills of the entry-level healthcare professionals is important for providing clinical competency and improving patient care. This study aimed to develop novel, innovative computer-based test (Inno-CBT) item types for application in the national examination of Korean healthcare professionals. This exploratory study was conducted from May 2021 to March 2022 by a team of faculty members from pharmacy schools in South Korea. A literature search using PubMed, Google Scholar, RISS, Web of Science, and KoreaMed was performed. Forum presentations, media articles, and previous reports by the Korea Health Personnel Licensing Examination Institute (KHPLEI) were included. Workshops were held, information and ideas were collected and conceptualized, and item types were designed, drafted, and refined. By repeating this process, the Inno-CBT item types were finalized. Forty-one Inno-CBT item types with 28 subtypes were developed. New digital technologies, such as a reactive responsive media interface, an animation insertion, multimedia embedding, and network surfing, were utilized in these novel types. It was anticipated that these Inno-CBT item types would effectively measure abilities in healthcare knowledge, problem-solving skills, and professional behaviors. Some potential barriers to implementing the Inno-CBT item types include item difficulty, operational unfamiliarity, complexity in scoring protocols, and network security. A variety of styles of novel Inno-CBT item types were developed to evaluate the multifaceted and in-depth professional abilities required for healthcare professionals. Prior to implementing these item types in the national examination, item validation and technical support should be conducted.


Evaluation of demineralised, freeze-dried, irradiated bone allografts in the treatment of osseous defects in the oral cavity.
Demineralised, freeze-dried bone allografts (DFDBA) have been used extensively by dentists in the treatment of periodontal and periapical osseous defects resulting from inflammatory diseases. Their use in India however, is limited by the availability of quality allografts and the high cost of imported alternatives. A study was conducted to assess the osteogenic potential of DFDBA prepared for the first time in India by the Tata Memorial Hospital (TMH) Tissue Bank. The DFDBA was used in the treatment of osseous defects after removal of periapical lesions associated with devitalised teeth in 10 healthy patients. At the 6-month recall visit all the patients showed a remarkable decrease in the grades of mobility, and 9 out of the 10 patients showed radiographic evidence of complete healing of the osseous defects with evidence of normal bony trabaeculae. These findings indicate that the indigenously prepared DFDBA is a cost effective, biocompatible material with osteogenic potential that can be used effectively in treating osseous defects of periapical lesions associated with non vital teeth.


Pap Testing in a High-Income Country with Suboptimal Compliance Levels: A Survey on Acceptance Factors among Sicilian Women.
Cervical cancer screening is uncommon, especially in low-income countries and among lower socioeconomic status people in high-income countries. The aims of this study were to examine the adherence of Sicilian women to Pap testing and to identify the determinants of this in a population with a secondary prevention attitude lower than high-income countries and the national average. A cross-sectional study called "Save Eva in Sicily" was conducted among all women aged 25⁻64 years, with a sample drawn by the list of general practitioners (GPs), using a proportional sampling scheme, stratified by age and resident population. The study outcome was performing a Pap test within the past three years. The association between the outcome and Pap test determinants was analyzed through a multivariable logistic regression. Among the 365 interviewed women, 66% (n = 243) had a Pap test during the last 3 years. On the other hand, 18% of the other women (n = 66) had performed at least one Pap test previously and 16% (n = 56) had never had a Pap test. In a multivariable model, GPs' advice (adjusted OR 2.55; 95% CI 1.57⁻4.14) and perceived susceptibility (adjusted OR 3.24; 95% CI 1.92⁻5.48) increased the likelihood of the execution of a Pap test. The "Save Eva in Sicily" study identified GP advice and perceived cancer severity as the main correlates of Pap testing among Sicilian women, producing evidence regarding how policy makers can increase compliance. Interventions to increase Pap test adhesion should focus on stimulating GPs to identify patients who regularly do not undergo it and to recommend testing on a regular basis to their patients.


Multidrug resistance-1 gene expression does not increase during tumor progression in the MGH-OGS murine osteosarcoma tumor model.
In addition to its possible role in drug resistance, expression of the multidrug resistance-1 gene may also be associated with a more malignant phenotype and tumor progression. This study evaluated its expression during tumor progression in the MGH-OGS transplantable murine osteosarcoma tumor model. Three variables of tumor progression were analyzed: tumor size, local recurrence, and metastasis. With a highly sensitive reverse transcription-polymerase chain reaction method, mRNA levels of multidrug resistance-1 were compared in primary tumors of different sizes. In addition, the levels were compared in primary, locally recurrent, and metastatic tumors isolated from individual mice. No significant difference was found in the levels of expression with increasing primary tumor size. In addition, the levels in primary, locally recurrent, and metastatic tumors were not significantly different. Our results indicate that--at least in the MGH-OGS tumor model, which is analogous to the majority of spontaneously occurring human osteosarcomas in that it has low levels of multidrug resistance-1/P-glycoprotein and is sensitive to doxorubicin--there is no evidence of upregulation of multidrug resistance-1 expression during tumor progression.


Significance of Baseline Ischemic Core Volume on Stroke Outcome After Endovascular Therapy in Patients Age ≥75 Years: A Pooled Analysis of Individual Patient Data From 7 Trials.
Age and infarct volume are strong predictors of outcome in patients with ischemic stroke who underwent endovascular therapy (EVT). We aimed to investigate the impact of ischemic core volume (ICV) on stroke outcome after EVT in elderly. Using the HERMES (Highly Effective Reperfusion Using Multiple Endovascular Devices) collaboration, a patient-level meta-analysis of 7 randomized trials in which patients were enrolled from December 2010 to April 2015) dataset, we categorized patients into those aged <75 and ≥75 years. ICV was calculated on computed tomography perfusion or magnetic resonance diffusion-weighted imaging. The association between ICV and the benefit of EVT over best medical treatment on outcome (modified Rankin Scale [mRS] at 90 days) and an ICV threshold for high likelihood (≥90%) of very poor outcome (mRS score ≥5) after EVT were investigated. A total of 899 patients who had baseline ICV data, 247 patients aged ≥75 years, of which 118 were randomized in the EVT arm. Patients aged ≥75 years required smaller ICV to achieve mRS score ≤3 than those aged <75 years in the EVT arm (median 10.7 mL versus 23.9 mL, P<0.001). In patients aged ≥75 years, modeling of outcome in both treatment arms revealed potential loss of effect for EVT at ICV of ≥50 mL or ≥85 mL for achieving mRS score ≤3 or ≤4, respectively. Treatment effect of EVT was significant in ICV <50 mL for mRS ≤3 (odds ratio 2.38, 95% confidence interval 1.35-4.22). ICV ≥132 mL was a threshold for high likelihood of very poor outcome after EVT. However, EVT still predicted at least 30% rate of mRS ≤3 at 150 mL ICV if near-complete or complete reperfusion was achieved. Baseline ICV has an impact on stroke outcome after EVT in the elderly, but elderly patients with large ICV may still benefit from EVT if near-complete or complete reperfusion is achieved. Young patients seem to benefit from EVT regardless of ICV status.


Effect of preservatives on microbial safety and quality of smoked blue catfish (Ictalurus furcatus) steaks during room-temperature storage.
The microbial safety and quality of smoked blue catfish (Ictalurus furcatus) steaks treated with antimicrobials and antioxidants were examined during 6-week ambient storage. Five pre-smoking soaking treatments were applied: 25% NaCl and 1% ascorbic acid for 30 min or 1h, 3% sodium lactate with or without 5% rosemary extract for 30 min, and 5% sorbic acid alone for 30 min. After smoking, cooled catfish steaks were packed and analyzed at 0, 2, 4, and 6 weeks of ambient storage. Neither Listeria nor Salmonella was recovered from the smoked catfish steaks. Significant reductions (P<0.05) in total plate counts were observed in all treated samples, with those treated with 3% sodium lactate carrying the lowest microbial load. The rosemary extract-treated samples were the most stable against oxidation. All treated smoked catfish steaks had water activities less than 0.85; however, neither pH nor water activity changed significantly within each treatment group during storage (P> or 0.05). In conclusion, smoking/cooking effectively reduced microbial populations, and the use of antimicrobial agents and antioxidants, particularly 3% sodium lactate, could aid the control of microbial safety during storage, resulting in safe products for up to 6 weeks without refrigeration.


[Do we have to remove a painless collar swelling along the carotid artery?].
Schwannoma are rare. We describe the clinical presentation, diagnostic workup and therapy in sympathetic chain schwannoma in a 54 year old patient. Besides the operative management the differential diagnosis of painless swelling at the carotid bifurcation are discussed.


Exon skipping creates novel splice variants of DMC1 gene in ruminants.
Disrupted meiotic cDNA1 (DMC1) recombinase plays a pivotal role in homology search and strand exchange reactions during meiotic homologous recombination. In the present study, full length coding sequence of DMC1 gene was sequence characterized for the first time from four ruminant species (cattle, buffalo, sheep and goat) and phylogenetic relationship of ruminant DMC1 with other eukaryotes was analyzed. DMC1 gene encodes a putative protein of 340 amino acids in cattle, sheep and buffalo and 341 amino acids in goat. A high degree of evolutionary conservation at both nucleotide and amino acid level was observed for the four ruminant orthologs. In cattle and sheep, novel alternatively spliced mRNAs with skipping of exons 7 and 8 (Transcript variant 1, TV1) were isolated in addition to the full length (FL) transcript. Novel transcript variants with partial skipping of exon 7 and complete skipping of exon 8 (Transcript variant 2, TV2) were found in sheep and goat. The presence of these variants was validated by amplifying cDNA isolated from testis tissue of ruminants using two oligonucleotides flanking the deleted region. To accurately estimate their relative proportions, real-time PCR was performed using primers specific for each variant. Expression level of DMC1-FL was significantly higher than that of TV1 in cattle and TV2 in goat (P < 0.05). Relative ratio for expression of DMC1-FL: TV1: TV2 in sheep was 6.78: 1.43: 1. In-silico analysis revealed presence of splice variants of DMC1 gene across other mammalian species underpinning the role of alternative splicing in functional innovation.


Preparation of cyanogen bromide fragments of MM, NN, and MN glycoproteins (glycophorins) from human erythrocyte membranes of single donors.
A procedure is described for the preparation of three cyanogen bromide fragments of the MM, NN, or MN glycoprotein (glycophorin) of the human erythrocyte membranes, from erythrocytes of single donors. The fragments are obtained in pure form and excellent yields by employing procedures which include proteolytic inhibitors during membrane processing, thorough delipidation of the glycoprotein, and CNBr cleavage conditions which lead to quantitative fragmentation without loss of carbohydrates. A phenol-urea extraction resolves the two glycopeptide fragments from the carbohydrate-free fragment. The two glycopeptides are further purified by Bio-Gel P-6 and P-100 chromatography. The three fragments include the amino terminal 8 residue glycopeptide, a large glycopeptide form the middle of the molecule which bears the Asn-linked oligosaccharide and 8--9 O-glycosidically linked units, and a carboxyl terminal, carbohydrate-free, approx. 50 residue fragment. Their amino acid and carbohydrate composition, and size, are in close agreement with the sequence data of Tomita, M., Furthmayr, H. and Marchesi, V.T. (Biochemistry (1978), 17, 4756--4770). The fragments represent three well delineated portions of the glycoprotein molecule.


Comparison of the Fluid Resuscitation Rate with and without External Pressure Using Two Intraosseous Infusion Systems for Adult Emergencies, the CITRIN (Comparison of InTRaosseous infusion systems in emergency medicINe)-Study.
Intraosseous infusion is recommended if peripheral venous access fails for cardiopulmonary resuscitation or other medical emergencies. The aim of this study, using body donors, was to compare a semi-automatic (EZ-IO®) device at two insertion sites and a sternal intraosseous infusion device (FASTR™). Twenty-seven medical students being inexperienced first-time users were randomized into three groups using EZ-IO and FASTR. The following data were evaluated: attempts required for successful placement, insertion time and flow rates with and without external pressure to the infusion. The first-pass insertion success of the EZ-IO tibia, EZ-IO humerus and FASTR was 91%, 77%, and 95%, respectively. Insertion times (MW ± SD) did not show significant differences with 17 ± 7 (EZ-IO tibia) vs. 29 ± 42 (EZ-IO humerus) vs. 33 ± 21 (FASTR), respectively. One-minute flow rates using external pressures between 0 mmHg and 300 mmHg ranged between 27 ± 5 to 69 ± 54 ml/min (EZ-IO tibia), 16 ± 3 to 60 ± 44 ml/min (EZ-IO humerus) and 53 ± 2 to 112 ± 47 ml/min (FASTR), respectively. Concerning pressure-related increases in flow rates, negligible correlations were found for the EZ-IO tibia in all time frames (c = 0.107-0.366; p ≤ 0.013), moderate positive correlations were found for the EZ-IO humerus after 5 minutes (c = 0.489; p = 0.021) and strong positive correlations were found for the FASTR in all time frames (c = 0.63-0.80; p ≤ 0.007). Post-hoc statistical power was 0.62 with the given sample size. The experiments with first-time users applying EZ-IO and FASTR in body donors indicate that both devices may be effective intraosseous infusion devices, likely suitable for fluid resuscitation using a pressure bag. Variations in flow rate may limit their reliability. Larger sample sizes will prospectively be required to substantiate our findings.


Effect of sucralfate and an aluminum hydroxide gel on gastric emptying of solids and liquids.
Our purpose was to investigate whether an aluminum-containing compound (sucralfate) and an aluminum-containing antacid (Amphojel; Wyeth Laboratories), both of which are commonly used in peptic ulcer disease, affect gastric emptying. Gastric emptying was studied in ten healthy subjects with the double isotope technique to assess simultaneous emptying rates of the solid and liquid components of a meal. 99mTechnetium sulfur colloid-labeled chicken liver served as the solid component and 111indium diethylenetriamine penta-acetic acid-labeled water was the liquid component. In a randomized, double-blind fashion, 1 gm sucralfate and 30 ml aluminum hydroxide gel were compared with placebo on separate days. Subjects ate the isotope-labeled test meal after dosing, and gastric emptying was monitored for 3 hours by a gamma-camera interfaced with a computer. There was no significant change in gastric emptying of either solids or liquids after sucralfate. The aluminum hydroxide gel slowed the gastric emptying rate for solids more than did the placebo, but this difference was significant only at the intervals of 165 and 180 minutes after the meal. We conclude that aluminum in the form of therapeutic doses of sucralfate does not delay gastric emptying of solids or liquids in normal subjects, while the larger amount of aluminum in therapeutic doses of the antacid gel has some slowing effect on gastric emptying of the solid components of a meal.


Pain Outcomes Following Mechanochemical Ablation vs Cyanoacrylate Adhesive for the Treatment of Primary Truncal Saphenous Vein Incompetence: The MOCCA Randomized Clinical Trial.
Endovenous thermal ablations (ETAs) are recommended as first-line treatment for truncal vein reflux, have a short recovery time, and are cost-effective. However, ETAs are associated with discomfort during tumescent anesthesia infiltration. To minimize discomfort, nonthermal, nontumescent ablation techniques had emerged in the form of mechanochemical ablation (MOCA) and cyanoacrylate adhesive injection (CAE). To assess pain scores immediately after truncal ablation using a 100-mm visual analog scale and 10-point number scale to compare pain-related outcomes following mechanochemical ablation vs cyanoacrylate adhesive treatment. The Multicenter Randomized II Clinical Trial Comparing Mechanochemical Ablation vs Cyanoacrylate Adhesive for the Treatment of Primary Truncal Saphenous Veins Incompetence study was a prospective multicenter randomized clinical trial conducted at 3 sites between November 2017 and January 2020. Inclusion criteria were primary great or small saphenous varicose veins; exclusion criteria included recurrent varicose veins, current deep venous thrombosis, or serious arterial disease. There were 392 participants screened, 225 were excluded, and 167 participants underwent randomization. Four participants did not receive allocated intervention and were included in the intention-to-treat analysis. Follow-up took place at 2 weeks, and 3, 6, and 12 months. Patients with primary truncal vein incompetence were randomized to receive either MOCA or CAE. The primary outcome measure was pain score immediately after completing truncal ablation using a 100-mm visual analog scale (VAS) and a 10-point number scale. Secondary outcome measures included degree of ecchymosis, occlusion rates, clinical severity, and generic and disease-specific quality of life (QoL) scores. Of 167 study participants, 99 (59.3%) were women, and the mean (SD) age was 56 (15.8) years. Overall, 155 truncal veins treated (92.8%) were great saphenous veins. Demographic data and baseline status were comparable between treatment groups. A total of 73 patients (47%) underwent adjunctive treatment of varicosities. Overall median (IQR) maximum pain score after truncal treatment was 23 mm (10-44) on the VAS and 3 (2-5) on the number scale, showing no significant difference in median (IQR) pain measured by VAS (MOCA, 24 [11.5-44.7] mm vs CAE, 20 [9.0-42.0] mm; P = .23) or by number scale (MOCA, 4 [2-5] vs CAE, 3 [2-4]; P = .18). Both groups demonstrated significant and comparable improvement in clinical severity, generic and disease-specific QoL scores, and complete occlusion rates. Four patients treated with CAE developed minor complications (superficial thrombophlebitis and thrombus extensions). To our knowledge, this was the first randomized clinical trial directly comparing nontumescent ablation techniques. The study demonstrated that the MOCA and CAE techniques have a similar periprocedural pain score. ClinicalTrials.gov Identifier: NCT03392753.


Leprosy and immunity: genetics and immune function in multiple case families.
Genetic susceptibility to infection with M. leprae was studied in 10 multiple case families of Australian Aborigines. Of the 87 members available for study, 24 had proven stable clinical leprosy which had been or was still being treated with diamino diphenyl sulphone. Evidence of contact with M. leprae in the remaining 63 members as assessed by ELISA to M. leprae sonicate and phenolic glycolipid (PGL) or by indirect immunofluorescence antibody assay was found in 78%, 64% and 71%, respectively. By contrast, in vitro assays of T cell function (LMAT and LTT) were less reliable indicators of exposure. Evidence was sought for possible linkages between human leucocyte antigen (HLA) or non-HLA genes and four marker phenotypes including clinical leprosy, clinical subtype of leprosy and lymphocyte transformation or leucocyte migration inhibition factor (LIF) production in response to M. leprae antigen. No associations were found with any particular HLA or non-HLA gene. On the other hand, sequential analysis of the data from the 10 families was strongly suggestive of a linkage between HLA haplotype and non-responsiveness to M. leprae as manifest by lack of LIF production but not lymphocyte transformation. The model which best fits the data is for a gene on chromosome 6 in close linkage with the HLA haplotype, with two alleles, autosomal recessive inheritance and penetrance of 90%. On this basis, it can be suggested that disease type (lepromatous leprosy) rather than disease susceptibility may be controlled by genes within or closely linked to the major histocompatibility gene complex.


On the potential use of two-photon polymerization to 3D print chromatographic packed bed supports.
The continuous quest for chromatographic supports offering kinetic performance properties superior to that of the packed bed of spheres has pushed the field to consider alternative formats such as for example monolithic and pillar array columns. This quest seems bound to culminate in the use of 3D printing technology, as this intrinsically offers the possibility to produce supports with a perfect uniformity and with a size and shape that is fully optimized for the chromatographic separation process. However, to be competitive with the current state-of-the-art, structures with sub-micron feature sizes are required. The present contribution therefore investigates the use of the 3D printing technology with the highest possible resolution available today, i.e., two-photon polymerization (2PP). It is shown that 2PP printing is capable of achieving the required ≤ 1 µm printing resolution. Depending on the laser scan speed, the lower limit through-pore size for a tetrahedral skeleton monolith with a theoretical 80% external porosity was found to be at 800 nm, when printing at a scan speed of 50 mm/s with a laser power of 10%. For a scan speed of 10 mm/s, the minimal through-pore size dropped to 500 nm. However, this very high resolution comes at the cost of excessively long printing times. The total printing time for a column volume equivalent to that of a typical nano-LC column (75 µm i.d. cylindrical tube with length L = 15 cm) has been determined to correspond to 330 and 470 h for the 50 mm/s and the 10 mm/s scan speed respectively. Other issues remaining to be solved are the need to clad the printed skeleton with a suitable mesoporous layer for chromatographic retention and the need to add a top-wall to the printed channels after the removal of the non-polymerized resin. It is therefore concluded that 2PP printing is not ready yet to replace the existing column fabrication methods.


Antigenicity and immunogenicity of recombinant proteins comprising African swine fever virus proteins p30 and p54 fused to a cell-penetrating peptide.
African swine fever (ASF) is a highly fatal swine disease threatening the global pig industry. Currently, vaccine is not commercially available for ASF. Hence, it is desirable to develop effective subunit vaccines against ASF. Here, we expressed and purified two recombinant fusion proteins comprising ASFV proteins p30 and p54 fused to a novel cell-penetrating peptide Z12, which were labeled as ZPM (Z12-p30-modified p54) and ZPMT (Z12-p30-modified p54-T cell epitope). Purified recombinant p30 and modified p54 expressed alone or fused served as controls. The transduction capacity of these recombinant proteins was assessed in RAW264.7 cells. Both ZPM and ZPMT exhibited higher transduction efficiency than the other proteins. Subsequently, humoral and cellular immune responses elicited by these proteins were evaluated in mice. ZPMT elicited the highest levels of antigen-specific IgG responses, cytokines (interleukin-2, interferon-γ, and tumor necrosis factor-α) and lymphocyte proliferation. Importantly, sera from mice immunized with ZPM or ZPMT neutralized greater than 85% of ASFV in vitro. Our results indicate that ZPMT induces potent neutralizing antibody responses and cellular immunity in mice. Therefore, ZPMT may be a suitable candidate to elicit immune responses in swine, providing valuable information for the development of subunit vaccines against ASF.


A Go-like protein in Drosophila melanogaster and its expression in memory mutants.
G proteins couple receptors for extracellular signals to several intracellular effector systems and play a key role in signalling transduction mechanisms. In particulate preparations of Drosophila melanogaster heads, only one substrate for pertussis toxin at 39-40 kd was detected. This substrate, which showed only one isoform when analysed by isoelectric focusing, was recognized by immunoblotting and immunoprecipitation techniques using a polyclonal antibody against the alpha subunit of the Go protein purified from bovine brain and can be thus considered as a Go-like protein. Antibodies obtained against a carboxy-terminal sequence of the alpha subunit of Go (but not of Gi1 or Gi2) and against an internal sequence shared by all the alpha subunits, were also able to cross-react with the alpha subunit of this protein in insects. We have also studied the Go-like protein in several D.melanogaster mutants, primarily in memory and learning mutants. In these mutants there was a sex-dependent enhancement in pertussis toxin-catalysed ADP-ribosylation with respect to the wild-type. This increase could be attributed in part to an increase in the alpha subunit of the Go-like protein, as revealed by immunoblotting with anti-Go alpha polyclonal antibody. This report constitutes the first evidence for the participation of a Go protein in learning and memory.


Uvulopalatopharyngoplasty: treatment of obstructive sleep apnea in neurologically impaired pediatric patients.
Bona fide obstructive sleep apnea is rare in the pediatric age group. Traditional surgical management for pediatric obstructive sleep apnea (OSA) is adenotonsillectomy alone, however, severely affected children may require uvulopalatopharyngoplasty (UPPP) or tracheostomy to relieve their obstruction. Children with OSA along with other medical maladies (e.g. cerebral palsy, down syndrome) pose an additional challenge to the otolaryngologist due to poor muscular tone and other medical problems which may complicate postoperative management. We report on 15 children (aged 23 months-13 years, mean 7.4 years), 12 with severe mental insufficiency, with documented OSA who underwent classical or modified UPPP. Twelve of 15 had clinical and/or objective improvement. We conclude that UPPP has a role in the management of neurologically-impaired children with OSA.


A single-center study of aminolevulinic acid and 417 NM photodynamic therapy in the treatment of moderate to severe acne vulgaris.
This article describes a single-center trial involving twenty-two patients with acne vulgaris. Blu-U light was used in all patients, while half were pre-treated with aminolevulinic acid. Preliminary results show promise for this treatment in mild to moderate inflammatory acne vulgaris.


Carpal tunnel volume determination by magnetic resonance imaging three-dimensional reconstruction.
Three-dimensional computer reconstruction of magnetic resonance images (MRI) of ten cadaveric specimens was used to determine carpal tunnel volume and carpal arch width. Magnetic resonance images-acquired data were compared with direct measurement of cadaveric carpal canal volume by means of a silicone-injection technique. Mean MRI three-dimensional reconstruction volume was 5.84 ml +/- 1.24 ml. Mean silicone-mold volume was 4.73 +/- 1.01 ml. A correction factor of 0.8161 was used to accurately calculate carpal tunnel volume from MRI-acquired data. There was no significant difference between calculated carpal tunnel volumes and silicone-mold volumes (p = 0.623), and there was a linear relationship between MRI-acquired volumes and silicone-mold volumes (correlation coefficient r = 0.97). Differences in MRI-volume determinations between observers were not significant (0.25 greater than or equal to p greater than 0.1). MRI three-dimensional reconstruction, a valid and reproducible technique for measuring carpal tunnel volume and dimensions, has considerable research potential for the evaluation of the relationship between the carpal canal and its contents before and after carpal tunnel release.


Polymeric iron chelators for enhancing 5-aminolevulinic acid-induced photodynamic therapy.
5-Aminolevulinic acid (5-ALA) is an amino acid that can be metabolized into a photosensitizer, protoporphyrin IX (PpIX) selectively in a tumor cell, permitting minimally invasive photodynamic diagnosis/therapy. However, some malignant tumor cells have excess intracellular labile iron and facilitate the conversion of PpIX into heme, which compromises the therapeutic potency of 5-ALA. Here, we examined the potential of chelation of such unfavorable intratumoral labile iron in photodynamic therapy (PDT) with 5-ALA hydrochloride, using polymeric iron chelators that we recently developed. The polymeric iron chelator efficiently inactivated the intracellular labile iron in cultured cancer cells and importantly enhanced the accumulation of PpIX, thereby improving the cytotoxicity upon photoirradiation. Even in in vivo study with subcutaneous tumor models, the polymeric iron chelator augmented the intratumoral accumulation of PpIX and the PDT effect. This study suggests that our polymeric iron chelator could be a tool for boosting the effect of 5-ALA-induced PDT by modulating tumor microenvironment.


Purification and identification of antigenic polypeptides of Sm and RNP antigens of goat liver.
A ribonucleoprotein complex containing Sm and RNP antigenic activity was isolated from goat liver. The sodium dodecyl sulfate polyacrylamide gel electrophoresis revealed the complex to contain four major polypeptides of 80,000, 70,000, 30,000 and 14,000 molecular weights. When the gels were probed for antigenic polypeptides by an enzyme-linked immunosorbent assay and fluorescent antibody method, anti-Sm sera were found to react with polypeptides of 14,000 and 30,000 molecular weights whereas anti-RNP sera recognized 70,000 and 80,000 molecular weight polypeptides with minor reactivity in the polypeptide of 14,000 molecular weight. Sera containing antibodies to both Sm and RNP reacted with all the four polypeptides.


Self-reported Race, Serum Creatinine, Cystatin C, and GFR in Children and Young Adults With Pediatric Kidney Diseases: A Report From the Chronic Kidney Disease in Children (CKiD) Study.
Recent reassessment of the use of race in estimated glomerular filtration rate (eGFR) in adults has instigated questions about the role of race in eGFR expressions for children. Little research has examined the associations of self-reported race with measured GFR (mGFR) adjusting for serum creatinine or cystatin C in children and young adults with chronic kidney disease (CKD). This study examined these associations and evaluated the performance of the previously published "U25" (under the age of 25 years) eGFR equations in a large cohort of children and young adults with CKD. Observational cohort study. Participants in the Chronic Kidney Disease in Children (CKiD) study including 190 Black and 675 non-Black participants contributing 473 and 1,897 annual person-visits, respectively. Self- or parental-reported race (Black, non-Black). Adjustment for serum creatinine or cystatin C, body size, and socioeconomic status. mGFR based on iohexol clearance. Linear regression with generalized estimating equations, stratified by age (<6, 6-12, 12-18, and ≥18 years) incorporating serum creatinine or serum cystatin C. Contrasting performance in different self-reported racial groups of the U25 eGFR equations. Self-reported Black race was significantly associated with 12.8% higher mGFR among children in regression models including serum creatinine. Self-reported Black race was significantly associated with 3.5% lower mGFR after adjustment for cystatin C overall but was not significant for those over 12 years. The results were similar after adjustment for body size and socioeconomic factors. The average of creatinine- and cystatin C-based U25 equations was unbiased by self-reported race groups. Small number of children < 6 years; lean body mass was estimated. Differences in the creatinine-mGFR relationship by self-reported race were observed in children and young adults with CKD and were consistent with findings in adults. Smaller and opposite differences were observed for the cystatin C-mGFR relationship, especially in the younger age group. We recommend inclusion of children for future investigations of biomarkers to estimate GFR. Importantly, for GFR estimation among those under 25 years of age, the average of the new U25 creatinine and cystatin C equations without race coefficients yields unbiased estimates of mGFR.


Caregiver demand and parent distress in juvenile rheumatic disease: the mediating effect of parent attitude toward illness.
Parents of youth with juvenile rheumatic diseases (JRD) often take on illness management responsibilities that can become burdensome, potentially resulting in poor parent adjustment outcomes. However, not all caregivers will experience increased distress as a result of variability in stress appraisals. The current study examined the role of parent illness attitudes in the relation between perceived caregiver demand and parental distress. Youth (N = 70) ages 7-18 years diagnosed with a JRD and their parents were recruited from a pediatric rheumatology clinic. Parents completed measures of caregiver demand, parental distress, and illness attitudes. Hierarchical regression revealed a relationship between caregiver demand and parental distress. A significant relationship was also found between caregiver demand and parent illness attitudes, as well as parent illness attitudes and parental distress. Thus, parent illness attitudes mediated the relationship between caregiver demand and parental distress. Techniques aimed at altering negative illness attitudes may help parents cope with their caregiving responsibilities.


[Medical treatment of symptomatic uterine leiomyomata in premenopausal woman].
The most frequent symptom with leiomyoma is menometrorrhagia. However, it can be responsible of pelvic pain, dysmenorrhea or urinary and digestive compression when it is particularly voluminous. If no therapy is able to have them disappear, various drugs may reduce their related symptoms. Tranexamic acid, non-steroidal anti-inflammatory drugs and high dose of oestrogen may be useful in the management of acute hemorrhagic disorders. Progestin, such as lynestrenol induces small reduction in leiomyoma volume and moderate increase in hemoglobin level before surgery. Pregnane and nor-pregnane may improve menstrual bleeding in short or mild delays. The use of GnRH agonists can reduce menstrual bleeding with hemoglobin recovery. Add-back therapy using tibolone seems interesting since secondary effects encountered with GnRH agonists may be reduced. Levonorgestrel-releasing intrauterine system is proven to reduce increased menstrual bleeding and restore hemoglobin level. Aminoglutethimide and fadrozole have been underevaluated to conclude when letrozole seems as efficient as GnRH agonists to reduce leiomyoma volume and provide less hotflushes. Anastrozol is associated with reduction in leiomyomata volume, pain and menstrual bleeding. Mifepristone reduces the size of uterine leiomyomata, improves symptomatology, but could be associated with development of endometrial hyperplasia. SPRM evaluated in females have shown to improve leiomyoma related symptomatology. Ulipristal could be useful to reduce leiomyoma related symptoms in short terms.


Regulators of G protein signaling attenuate the G protein-mediated inhibition of N-type Ca channels.
Regulators of G protein signaling (RGS) proteins bind to the alpha subunits of certain heterotrimeric G proteins and greatly enhance their rate of GTP hydrolysis, thereby determining the time course of interactions among Galpha, Gbetagamma, and their effectors. Voltage-gated N-type Ca channels mediate neurosecretion, and these Ca channels are powerfully inhibited by G proteins. To determine whether RGS proteins could influence Ca channel function, we recorded the activity of N-type Ca channels coexpressed in human embryonic kidney (HEK293) cells with G protein-coupled muscarinic (m2) receptors and various RGS proteins. Coexpression of full-length RGS3T, RGS3, or RGS8 significantly attenuated the magnitude of receptor-mediated Ca channel inhibition. In control cells expressing alpha1B, alpha2, and beta3 Ca channel subunits and m2 receptors, carbachol (1 microM) inhibited whole-cell currents by approximately 80% compared with only approximately 55% inhibition in cells also expressing exogenous RGS protein. A similar effect was produced by expression of the conserved core domain of RGS8. The attenuation of Ca current inhibition resulted primarily from a shift in the steady state dose-response relationship to higher agonist concentrations, with the EC50 for carbachol inhibition being approximately 18 nM in control cells vs. approximately 150 nM in RGS-expressing cells. The kinetics of Ca channel inhibition were also modified by RGS. Thus, in cells expressing RGS3T, the decay of prepulse facilitation was slower, and recovery of Ca channels from inhibition after agonist removal was faster than in control cells. The effects of RGS proteins on Ca channel modulation can be explained by their ability to act as GTPase-accelerating proteins for some Galpha subunits. These results suggest that RGS proteins may play important roles in shaping the magnitude and kinetics of physiological events, such as neurosecretion, that involve G protein-modulated Ca channels.


Effect of treatment with an overheated dry-saturated steam vapour disinfection system on multidrug and extensively drug-resistant nosocomial pathogens and comparison with sodium hypochlorite activity.
The development of portable steam generators has made disinfection of the environment more practical. This study assessed the "in vitro" ability of an overheated dry-saturated steam vapour system to kill multidrug and extensively-drug resistant nosocomial pathogens, defining the antimicrobial spectrum and the contact times compared with the activity of sodium hypochlorite. The antibacterial efficacy of the overheated dry-saturated steam vapour system and of sodium hypochlorite against nosocomial pathogen isolates: extensively drug-resistant Acinetobacter baumannii, Pseudomonas aeruginosa, carbapenemase-producing Klebsiella pneumoniae, methicillin-resistant Staphylococcus aureus, high-level aminoglycoside-resistant Enterococcus faecalis, Candida parapsilosis and Aspergillus fumigatus were assessed using a surface time-kill test carried out on glass surfaces, with or without bovine serum albumin (BSA). The bactericidal activity of the overheated dry-saturated steam vapour system was observed at 180 °C after 5 min contact with or without BSA, using an initial inoculum of 10(9) CFU/mL. To reduce C. parapsilosis and A. fumigatus counts (from 10(7) CFU/mL), a longer contact time was necessary (7 min). In vitro tests with sodium hypochlorite at 5 % in the absence of an organic substance also resulted in an overall reduction in bacterial counts (from 10(9) CFU/mL) after 5 min of treatment. For mycotic challenge (10(7) CFU/mL), a longer contact time was necessary (7 min). In the presence of an organic substance, after 5 min, the hypochlorite reduced the viable count from 10(9) to 10(5) CFU/mL for all bacterial strains except E. faecalis that showed a reduction of 2 log units (10(9) to 10(7) CFU/mL). For C. parapsilosis and A. fumigatus, a 2 log unit reduction was observed after 7 min. Steam disinfection of environmental surfaces using a portable steam generator is a practical and effective method that is not affected by the presence of organic matter.


Initial experience with a free, high-volume, low-dose CT lung cancer screening program.
The National Lung Screening Trial demonstrated a significant mortality benefit for patients at high risk for lung cancer undergoing serial low-dose CT. Currently, the National Comprehensive Cancer Network and several United States-based professional associations recommend CT Lung screening for high-risk patients. In the absence of established reimbursement, the authors modeled and implemented a free low-dose CT lung cancer screening program to provide equitable access to all eligible patients. Elements of the program reported in this article include a decentralized referral network, centralized program coordination, structured reporting, and a patient data management system. The experience and initial results observed in this clinical setting closely match the performance metrics of the National Lung Screening Trial with regard to cancer detection and incidental findings rates. To eliminate health care disparities a vigorous lobbying effort will be needed to expedite reimbursement and make CT lung screening equally available to all patients at high-risk.


Regional dysfunction by equilibrium radionuclide angiocardiography: a clinicopathologic study evaluating the relation of degree of dysfunction to the presence and extent of myocardial infarction.
The relation of degree of regional wall motion abnormality by equilibrium radionuclide angiocardiography to the presence and mural extent of regional necrosis or scar at autopsy was evaluated in 23 autopsy patients who had a history of myocardial infarction and had equilibrium radionuclide angiocardiography within 40 days of death. Of the 228 regions evaluated by equilibrium radionuclide angiocardiography, 135 had abnormal regional wall motion and 102 (76%) of these 135 regions had evidence of myocardial infarction at autopsy. The overall sensitivity, specificity and predictive values of regional wall motion abnormality for regional necrosis or scar were 69, 59 and 76%, respectively. Of the 33 false positive regions, 20 (61%) had severe narrowing of the coronary artery supplying that region, 13 (39%) were adjacent to a region with a myocardial infarction and almost half (16 [48%]) were in the lateral wall. Eighty-three (36%) of the 228 regions were akinetic or dyskinetic, 52 (23%) were hypokinetic and 93 (41%) were normal. Sixty-three (76%) of the 83 akinetic/dyskinetic segments had transmural myocardial infarction at autopsy, 14 (17%) had nontransmural myocardial infarction and only 6 (7%) contained no necrosis or scar. In contrast, 14 (27%) of 52 hypokinetic segments had transmural myocardial infarction, 11 (21%) had nontransmural myocardial infarction and 27 (52%) were normal. Thus, the most severe regional wall motion abnormality (akinesia/dyskinesia) almost always indicates regional myocardial infarction which is usually transmural whereas less severe dysfunction (hypokinesia) is not necessarily associated with regional necrosis or scar. The severity of regional dysfunction must be considered if equilibrium radionuclide angiocardiography is used to evaluate the presence and mural extent of myocardial infarction within a region.


Control of blood capillary networks and holes in blood-brain barrier models by regulating elastic modulus of scaffolds.
The blood-brain barrier (BBB) is a type of capillary network characterized by a highly selective barrier, which restricts the transport of substances between the blood and nervous system. Numerous in vitro models of the BBB have been developed for drug testing, but a BBB model with controllable capillary structures remains a major challenge. In this study, we report for the first time a unique method of controlling the blood capillary networks and characteristic holes formation in a BBB model by varying the elastic modulus of a three-dimensional scaffold. The characteristic hole structures are formed by the migration of endothelial cells from the model surface to the interior, which have functions of connecting the model interior to the external environment. The hole depth increased, as the elastic modulus of the fibrin gel scaffold increased, and the internal capillary network length increased with decreasing elastic modulus. Besides, internal astrocytes and pericytes were also found to be important for inducing hole formation from the model surface. Furthermore, RNA sequencing indicated up-regulated genes related to matrix metalloproteinases and angiogenesis, suggesting a relationship between enzymatic degradation of the scaffolds and hole formation. The findings of this study introduce a new method of fabricating complex BBB models for drug assessment.


Parent artery stenting as a rescue management for stretched coils during cerebral aneurysms embolization: Report of three cases and review of literature.
Displacement of a stretched coil into the parent artery during intracranial aneurysm coiling is a challenging situation where the risk of acute intravascular thrombosis might be a life-threatening condition. The usual way of management is coil snaring, yet in some cases, it might not be feasible to retrieve the coil. Parent artery rescue stenting had already been described as a way of management in acutely thrombosed parent arteries during aneurysm coiling. We present three cases with an inadvertent displacement of the unraveled coils into the parent artery for which rescue stenting was carried out to crush the coil against the vessel wall aiming to eliminate its thrombogenic effect. Our preliminary experience is that rescue stenting of the parent artery for stretched coil could be a convenient effective option particularly in case of failed/risky snaring with no notable immediate or long-term complications. We review the reported cases of stretched coils with or without further unraveling and fracture and discuss the possible consequences, salvage methods, and clinical outcomes. Neurointerventionists should be aware of this complication and get acquainted with bailout strategies.


Cost effectiveness of first-line pemetrexed plus platinum compared with other regimens in the treatment of patients with nonsquamous non-small cell lung cancer in the US outpatient setting.
This retrospective observational study evaluated cost effectiveness of first-line treatment of advanced nonsquamous non-small cell lung cancer (NSCLC) with pemetrexed/platinum (Pem/Plat) relative to paclitaxel/carboplatin (Pac/Carbo) and paclitaxel/carboplatin/bevacizumab (Pac/Carbo/Bev). Patients initiating first-line treatment from 2006 to 2009 were identified in electronic medical records of 20 US oncology practices. Pem/Plat patients were matched 1:1 on important characteristics with Pac/Carbo and Pac/Carbo/Bev patients and followed for 1 year to assess progression, survival, and costs. Bootstrapping was used to calculate the probability of falling within quadrants of the incremental cost-effectiveness plane. Kaplan-Meier analysis and Cox proportional hazards regression modeling were also performed. Three hundred Pem/Plat patients (mean age, 67.6 years; male, 56.0%; PS 0/1, 71.0%) were matched with 300 patients in the other cohorts. Median PFS was 134 days (Pem/Plat) versus 106 days (Pac/Carbo) (hazard ratio [HR]: 0.67, P < 0.001) and 126 days (Pac/Carbo/Bev) (HR: 0.68, P < 0.001). Median OS was 298 days (Pem/Plat) versus 218 days (Pac/Carbo) (HR: 0.88, P = 0.08) and 271 days (Pac/Carbo/Bev) (HR: 0.93, P = 0.31). Pem/Plat therapy costs were higher versus Pac/Carbo ($21,841 higher PFS; $19,137 higher OS; P ≤ 0.05) and lower versus Pac/Carbo/Bev ($15,160 lower PFS; $19,946 lower OS; P ≤ 0.05). Pem/Plat had a greater probability of higher costs/higher effectiveness versus Pac/Carbo (PFS, 90.1%; OS, 96.3%) and lower costs/higher effectiveness versus Pac/Carbo/Bev (PFS, 69.5%; OS, 85.0%). Pem/Plat had higher cost and effectiveness than Pac/Carbo; depending on a payer's or society's willingness to pay, Pem/Plat may be considered cost effective compared with Pac/Carbo. Pem/Plat yielded greater effectiveness with lower costs than Pac/Carbo/Bev.


Characterization and biocontrol potential of a naturally occurring isolate of Metarhizium pingshaense infecting Conogethes punctiferalis.
An entomopathogenic fungus was isolated from an infected larva of Conogethes punctiferalis (Guenée) (Crambidae: Lepidoptera), a highly polyphagous pest recorded from more than 120 plants and widely distributed in Asia and Oceanic countries. The fungus was identified as Metarhizium pingshaense Q.T. Chen & H.L. Guo (Ascomycota: Hypocreales) based on morphological characteristics and molecular studies. Scanning electron microscopic studies were conducted to study the infection of C. punctiferalis by M. pingshaense. Bioassay studies with purified conidial suspension proved that the isolate was highly virulent to C. punctiferalis, causing more than 86 % mortality to fifth instar larvae at 1 × 108 spores/mL, under laboratory conditions. The median lethal concentration (LC50) of the fungus against late instar larvae was 9.1 × 105 conidia/mL and the median survival time (MST) of late instar larvae tested at the doses of 1 × 108 and 1 × 107 conidia/mL were 4.7 and 6.4 days, respectively. The optimal temperature for fungal growth and sporulation was found to be 25 ± 1 °C. This is the first report of M. pingshaense naturally infecting C. punctiferalis. Isolation of a highly virulent strain of this fungus holds promise towards development of a potential mycoinsecticide against this pest.


Percutaneous vs. totally implantable catheters in home parenteral nutrition.
The technique of the implementation of Home Parenteral Nutrition (HPN) is improving continuously so carrying minimum risk of technical complications and supplying maximum comfort for the patient. For example the HPN benefits of the recent availability of Ethil-Vinil-Acetate (EVA) bags that permit the contemporary administration of all nutrients, lipids included, and of infusion pumps which are lighter, safer and more versatile and which have rechargeable batteries. Some new types of completely implantable catheters with a subcutaneous reservoir present a better rationale compared with complications and with patient's compliance in respect of traditional percutaneous catheters used in HPN. We wanted to verify these presuppositions in a retrospective study with a completely implantable catheter, Port-A-Cath (PAC) Pharmacia, with a group of six patients already under HPN for a period of 901 patient-days with a percutaneous catheter. We compared the two methods of treatment after 1114 patient-days with the PAC. Concerning complications, we have three catheter related sepsis (3.3 1000 days) with percutaneous catheter and 1 sepsis (0.9 1000 days) with the PAC. We also had one catheter obstruction in a patient with the PAC implanted in the Inferior Vena Cava. All the patients accepted the new technique and even if they did not have the same motivation, all of them particularly appreciated the possibility of the avoidance of any external device. Our experience leads us to report that the Port-A-Cath system may be useful in long-term parenteral nutrition but other research is needed to confirm its rationale.


Human posterior parietal cortex maintains color, shape and motion in visual short-term memory.
We used functional magnetic resonance imaging (fMRI) to investigate the neural substrate of visual short-term memory for objects defined by features processed in the dorsal and the ventral visual streams. Here we adopted the conventional delayed recognition task, whereas in addition to the more commonly used visual features of color and shape, motion direction was applied to define an item. Our behavioral results indicated that the capacity limit of visual short-term memory of motion direction was approximately two, which was significantly lower than those of color and shape, about three or four. We also found that storage capacity was significantly reduced when subjects were required to retain all three features superimposed in space. Meanwhile, fMRI results revealed that activity in the posterior part of the superior parietal lobe was memory-load dependent for all three features indicating that it collects and stores visual information from both the two visual processing streams, whereas the anterior part was load dependent only for motion.


Molecular genetic studies of complex phenotypes.
The approach to molecular genetic studies of complex phenotypes evolved considerably during the recent years. The candidate gene approach, which is restricted to an analysis of a few single-nucleotide polymorphisms (SNPs) in a modest number of cases and controls, has been supplanted by the unbiased approach of genome-wide association studies (GWAS), wherein a large number of tagger SNPs are typed in many individuals. GWAS, which are designed on the common disease-common variant hypothesis (CD-CV), identified several SNPs and loci for complex phenotypes. However, the alleles identified through GWAS are typically not causative but rather in linkage disequilibrium (LD) with the true causal variants. The common alleles, which may not capture the uncommon and rare variants, account only for a fraction of heritability of the complex traits. Hence, the focus is being shifted to rare variants-common disease (RV-CD) hypothesis, surmising that rare variants exert large effect sizes on the phenotype. In conjunctional with this conceptual shift, technologic advances in DNA sequencing techniques have dramatically enhanced whole genome or whole exome sequencing capacity. The sequencing approach affords identification of not only the rare but also the common variants. The approach-whether used in complementation with GWAS or as a stand-alone approach-could define the genetic architecture of the complex phenotypes. Robust phenotyping and large-scale sequencing studies are essential to extract the information content of the vast number of DNA sequence variants (DSVs) in the genome. To garner meaningful clinical information and link the genotype to a phenotype, the identification and characterization of a large number of causal fields beyond the information content of DNA sequence variants would be necessary. This review provides an update on the current progress and limitations in identifying DSVs that are associated with phenotypic effects.


Morphotaxonomical description of three new species of Myxobolus Bütschli, 1882 (Myxozoa: Myxosporea: Bivalvulida) from edible freshwater fishes of West Bengal, India.
Three new species of Myxobolus are described from the mucous membrane around gill lamellae of carps of West Bengal. The new species have been named as M. muralidharani sp. n., M. nilimae sp. n. from Labeo rohita, and M. harpreetae sp. n. from Labeo bata respectively. Spores of M. muralidharani sp. n. measured 13.84 ± 0.049 (13-14) × 4.95-6 (5.35) µm, with two elongated equal sized polar capsules. Spores of M. nilimae sp. n. measured 15.9-17.1 (16.65) µm × 6.2-7.5 (6.9) µm, with two equal petal shaped polar capsules, 9.0-11 (10.4) µm × 3-3.5 (3.16) µm. In contrast to aforementioned two new species, M. harpreetae sp. n. had two unequal polar capsules, 8.7-9.2 (9.149) µm × 2.9-4.0 (3.45) µm and 7.6-8.3 (7.94) µm × 2.8-3.3 (2.9) µm in each spore, 11.4-13.8 (13.2) µm × 4.9-7.8 (6.51) µm.


Chitosan-coated PLGA nanoparticles for the nasal delivery of ropinirole hydrochloride: In vitro and ex vivo evaluation of efficacy and safety.
Nose-to-brain delivery is an attractive route for direct drug delivery to the central nervous system (CNS), avoiding hepatic first-pass metabolism and solving blood-brain barrier passage issues. Therefore, the aim of the present study was the development of PLGA and PLGA/chitosan (chit) nanoparticles (NPs) with mucoadhesive properties, able to encapsulate ropinirole hydrochloride (RH), an anti-Parkinsonian dopaminergic agonist, and suitable to promote RH delivery across the nasal mucosa. NPs produced by nanoprecipitation showed spherical shape and a mean average size of 98.8 nm and 468.0 nm (PLGA and PLGA/chit, respectively). RH loaded PLGA/chit NPs showed a complete release of the drug in simulated nasal electrolyte solution (SNES) over the period of 24 h and increased the permeation of RH through sheep nasal mucosa by 3.22-fold in comparison to PLGA NPs. None of RH loaded NPs induced hemolysis in whole blood or the production of reactive oxygen species (ROS) in Raw 264.7 cells. On their turn, PLGA/chit NPs decreased cell viability of Raw 264.7 cells and Peripheral Blood Mononuclear Cells (PBMCs) in a concentration-dependent manner. These results revealed that, particularly PLGA/chit NPs, could be a valuable carrier for the delivery of RH to the CNS, opening a new path for Parkinson's disease therapy.


Enantio- and diastereoselective synthesis of piperidines by coupling of four components in a "one-pot" sequence involving diphenylprolinol silyl ether mediated Michael reaction.
An efficient, asymmetric, four-component, one-pot synthesis of highly substituted piperidines with excellent diastereo- and enantioselectivity was established through the diphenylprolinol silyl ether mediated Michael reaction of aldehyde and nitroalkene, followed by the domino aza-Henry reaction/hemiaminalization reaction and a Lewis acid mediated allylation or cyanation reaction. All carbons of the piperidine ring are substituted with different groups, and its five contiguous stereocenters are completely controlled in both relative and absolute senses.


Chitosan-based electrospun nanofibers for encapsulating food bioactive ingredients: A review.
Today, society has been more aware of healthy food products and related items containing bioactive compounds, which potentially contribute to human health. Unfortunately, the long-term stability and bioactivity of biologically active compounds against environmental factors compromise their target and effective action. In this way, lab-designed vehicles, such as nanoparticles and nanofibers, provide enough properties for their preservation and suitable delivery. Here, the electrospinning technique acts as an effective pathway for fabricating and designing nanofibers for the entrapments of biomolecules, in which several biopolymers such as proteins, polysaccharides (e.g., maltodextrin, agarose, chitosan), silk, among others, can be used as a wall material. It is likely that chitosan is one of the most employed biomaterials in this field. Therefore, in this review, we reveal the latest advances (over the last 2-3 years) in designing chitosan-based electrospun nanofibers and nanocarriers for encapsulation of bioactive compounds, along with the key applications in smart food packaging as well. Key findings and relevant breakthroughs are a priority in this review to provide a cutting-edge analysis of the literature. Finally, particular attention has been paid to the most promising developments.


Unusual ultrasound finding of patent ductus arteriosus in a preterm infant.
Patency of the ductus arteriosus (PDA) is a common finding in small premature infants. Recently pulsed-Doppler-cross sectional echocardiography (PD-CSE) has been successfully used in these patients. We report a case of a premature infant with an unusual PD-CSE pattern.


Automated high-performance cIMT measurement techniques using patented AtheroEdge™: a screening and home monitoring system.
The evaluation of the carotid artery wall is fundamental for the assessment of cardiovascular risk. This paper presents the general architecture of an automatic strategy, which segments the lumen-intima and media-adventitia borders, classified under a class of Patented AtheroEdge™ systems (Global Biomedical Technologies, Inc, CA, USA). Guidelines to produce accurate and repeatable measurements of the intima-media thickness are provided and the problem of the different distance metrics one can adopt is confronted. We compared the results of a completely automatic algorithm that we developed with those of a semi-automatic algorithm, and showed final segmentation results for both techniques. The overall rationale is to provide user-independent high-performance techniques suitable for screening and remote monitoring.


MR demonstration of spontaneous acute epidural hematoma of the thoracic spine.
Two patients with spontaneous epidural hematoma of the thoracic spine are presented. The magnetic resonance (MR) examination performed within the first hours following the onset of symptoms demonstrated an epidural elongated lesion impinging on the spinal cord, compatible with hematoma. In one of the patients this finding was surgically confirmed. The second patient improved under steroid treatment. The MR findings were highly suggestive of the pathological nature of the lesion. The MR examination should replace other diagnostic procedures, such as computerised tomography (CT) and myelography.


Transcriptional activation of H- and N-ras oncogenes in human cervical cancer.
Overexpression of p21 protein has been detected in human cervical cancer. However, to date, there are no data on the differential activation of the three ras genes at the transcriptional level in cervical lesions. The purpose of this study was to evaluate the quantitative and qualitative changes of expression of the ras family genes in the development of human cervical cancer. The expression of ras mRNA levels in 35 human cervical specimens [11 normal cervix, 15 cervical intraepithelial neoplasia (CIN), 9 cervical cancer] was examined using the RT-PCR technique. In addition, we studied the incidence of point mutations in codon 12 of each ras gene using RFLP analysis and human papilloma virus (HPV) status. The transcript levels for H-ras and N-ras were significantly higher in cancer cases compared to normal cervical tissues (P=0.0002 and P=0.001, respectively) and CIN lesions (P<0.0001 and P=0.002, respectively). The transcript levels for K-ras were similar in normal cervical tissue, CIN and cervical cancer. A strong positive correlation was found between H- and N-ras expression (P=0.001) and no correlation between H- and K- or N- and K-ras expression. Point mutations were detected only in three samples, located in codon 12 of K-ras gene. No relationship was found between expression levels of each ras gene and the presence of HPV. Our findings indicate the expression pattern of the three ras genes in cervical tissue and the involvement of H- and N-ras up-regulation in the pathogenesis of cervical cancer independent of HPV infection.


The use of nylon pouches to prevent cellular attachment to implanted materials.
A nylon pouch system has been developed to permit the in vivo exposure of implantable materials to tissue fluids without complications arising from cellular attachment or from the bacterial attack. SEM observations have indicated that the pouches were effective in reducing the ingress of bacteria as well as reducing, and in some cases eliminating, cell infiltration through their mesh structure. Over a 7 d implantation period, the exterior surfaces of the nylon pouches were heavily infested with microorganisms but there was minimal growth of bacteria within the pouches. Non-infected pouches that were implanted for up to 25 wk showed heavy deposits of cellular matter on the external surfaces of the pouches and minimal deposits within the pouches.


[Binding of cytosolic complexes of estradiol analogs with cell nuclei from the rabbit uterus].
The relative affinities of estrogen-receptor complexes for rabbit uterine nuclei were measured, using a newly developed technique. The low ligand specificity of this interaction was established.


Switching algorithms: from one immunomodulatory agent to another.
In spite of the availability of six disease-modifying treatments for multiple sclerosis, a significant minority of patients fail to respond adequately to treatment. Switching immunomodulatory therapy is a potentially useful treatment strategy in such patients. Several factors contribute to the need to switch between immunomodulatory treatments, including the variable response to drug treatment, the timing and choice of therapy, disease severity, and the occurrence of neutralising antibodies. Guidelines have been proposed to define treatment response, integrating both clinical and imaging criteria. Several observational studies, principally evaluating a switch from beta-interferons to glatiramer acetate, have demonstrated that switching treatments is both safe and effective in patients with inadequate control of disease activity or who are experiencing unacceptable side effects with their original treatment. A treatment algorithm is proposed for decision-making when switching therapies appears warranted.


Gait analysis for poststroke rehabilitation: the relevance of biomechanical analysis and the impact of gait speed.
Many stroke survivors have walking limitations. The results of gait training in individuals who have had strokes are characterized by large confidence intervals for mean differences in gait parameters. An individualized approach to therapy is needed, based on personalized gait pattern indicators and sensorimotor impairments. Three-dimensional gait analysis can help clinicians design the best locomotor training strategy for their patients, and can determine whether a patient is responding to the chosen intervention. Spatiotemporal parameters allow the characterization of the gait of hemiparetic patients but, used alone, they do not allow the cause of the deviations to be inferred.


New species of Anthurium Schott (Araceae) from the Kõkõi Eujã Natural Traditional Reserve of the Pacific coast, Cauca Department, Colombia.
The Kõkõi Eujã Natural Traditional Reserve was created in 2019 to protect the golden poison frog (Phyllobates terribilis Myers, Daly & Malkin, 1978) in the Cauca Department of Colombia. As part of the biodiversity inventory of the reserve a new species of Anthurium with scandent habit was discovered. The new species is endemic to Colombia and it is more similar to A. caldodsonii Croat, A. boekei Croat, and A. scandens (Aubl.) Engl., but differs by having widely lanceolate leaves with acuminate apex, cuneate base, and acrodromous venation with three pairs of basal veins.


Restricted weekend service inappropriately delays discharge after acute myocardial infarction.
Early discharge after myocardial infarction is safe and feasible. Factors that delay discharge need to be identified in order to improve care and reduce bed occupancy. To investigate the potential of the restricted weekend service that operates in most hospitals to delay patient discharge. Prospective cohort study. 2541 consecutive patients with acute myocardial infarction admitted to the coronary care unit of three local district hospitals over a 12 year period. Clinical factors affecting the duration of stay were age, sex, and severity of infarction. Thus older patients and women stayed significantly longer, as did patients with enzymatically large infarcts. Day of week also had an important influence on duration of stay. Discharge occurred most often on a Friday (p = 0.006) and least often over the weekend (p = 0.0001). Patients were preferentially discharged on a Friday if the length of stay was more than 72 hours. Thus patients admitted on a Sunday or Monday were usually discharged the following Friday, corresponding to a median duration of stay of five or four days, respectively. For patients admitted on Tuesday to Saturday, weekend discharge was avoided and the median duration of stay was six to eight days. For patients with acute myocardial infarction, discharge decisions were influenced appropriately by clinical indicators of risk, but inappropriately by the day of the week. Thus weekend discharge was generally avoided, leading to variations in length of stay that were largely determined by the day of the week on which admission occurred rather than clinical need.


Molecular detection, quantification, and isolation of Streptococcus gallolyticus bacteria colonizing colorectal tumors: inflammation-driven potential of carcinogenesis via IL-1, COX-2, and IL-8.
Colorectal cancer (CRC) has long been associated with bacteremia and/or endocarditis by Streptococcus gallolyticus member bacteria (SGMB) but the direct colonization of SGMB along with its molecular carcinogenic role, if any, has not been investigated. We assessed the colonization of SGMB in CRC patients with history of bacteremia (CRC-w/bac) and without history of bacteremia (CRC-wo/bac) by isolating SGMB from feces, mucosal surfaces of colorectum, and colorectal tissues and detecting SGMB DNA, via PCR and in situ hybridization (ISH) assays targeting SodA gene in colorectal tissues. Moreover, mRNA of IL1, IL-8, COX-2, IFN-γ, c-Myc, and Bcl-2 in colorectal tissues of studied groups was assessed via ISH and RT-PCR. SGMB were found to be remarkably isolated in tumorous (TU) and non-tumorous (NTU) tissues of CRC-w/bac, 20.5% and 17.3%, and CRC-wo/bac, 12.8% and 11.5%, respectively while only 2% of control tissues revealed SGMB (P < 0.05); such contrast was not found in mucosal and fecal isolation of SGMB. The positive detection of SGMB DNA in TU and NTU of CRC-w/bac and CRC-wo/bac via PCR, 48.7%, 35.9%, 32.7%, and 23%, respectively, and ISH, 46.1%, 30.7%, 28.8%, and 17.3%, respectively, was higher than in control tissues, 4 and 2%, respectively (P < 0.05). SGMB count measured via quantitative PCR of SGMB DNA in terms of copy number (CN), in TU and NTU of CRC-w/bac and CRC-wo/bac, 2.96-4.72, 1.29-2.81, 2.16-2.92, and 0.67-2.07 log10 CN/g respectively, showed higher colonization in TU than in NTU and in CRC-w/bac than in CRC-wo/bac (P < 0.05). The PCR-based mRNA ratio and ISH-based percentage of positively stained cells of IL-1, 1.77 and 70.3%, COX-2, 1.63 and 44.8%, and IL-8, 1.73 and 70.3%, respectively, rather than IFN-γ, c-Myc, and Bcl-2, were higher in SGMB positive patients than in control or SGMB negative patients (P < 0.05). The current study indicated that colorectal cancer is remarkably associated with SGMB; moreover, molecular detection of SGMB in CRC was superior to link SGMB with CRC tumors highlighting a possible direct and active role of SGMB in CRC development through most probably inflammation-based sequel of tumor development or propagation via, but not limited to, IL-1, COX-2, and IL-8.


Bioreversible quaternary N-acyloxymethyl derivatives of the poorly soluble tertiary amine Lu 28-179--synthesis, pharmaceutical chemical characterization and bioavailability studies in dogs.
Quaternary prodrug types of poorly water-soluble tertiary amines have been shown to possess significantly enhanced solubilities as compared to the parent amine. In the present study, the N-acyloxymethylation approach to improve the aqueous solubility of Lu 28-179 a tertiary amine exhibiting an intrinsic solubility in the nanomolar range, have been investigated. The acetyl-, propanoyl-, butanoyl-, isobutanoyl- and pivaloyloxymethyl derivatives were isolated as chloride salts and the aqueous solubilities (S) far exceeded that of the parent tertiary amine (S(0)). S/S(0) ratios in the range 2-4 x 10(6) were found for the most soluble prodrugs. The prodrugs were reasonable stable to hydrolysis in aqueous buffer solutions (pH 0.1-7.4), but susceptible to undergo enzyme-mediated regeneration of Lu 28-179 after incubation in human plasma, simulated intestinal fluid and duodenum juice from pigs and dogs. Despite promising in vitro properties the prodrugs were unable to improve the oral bioavailability of Lu 28-179 as compared to that obtained after administration of a reference formulation of the parent drug in the dog.