Use of a lensed fiber for a large-field-of-view, high-resolution, fiber-scanning microendoscope.
We report the application of a lensed fiber to a miniaturized fiber raster scanner in order to reduce the fiber's output beam size, thereby allowing for a compact and flexible endoscope capable of a large field of view (FOV) and high spatial resolution. For a proof of principle, the fabricated lensed fiber scanner is paired with a miniaturized gradient-index assembly to achieve a one-photon lateral resolution of 1.1 μm with a FOV that has a diameter of 440 μm.


Mitochondrial-derived peptides in aging and age-related diseases.
A decline in mitochondrial quality and activity has been associated with normal aging and correlated with the development of a wide range of age-related diseases. Here, we review the evidence that a decline in the levels of mitochondrial-derived peptides contributes to aging and age-related diseases. In particular, we discuss how mitochondrial-derived peptides, humanin and MOTS-c, contribute to specific aspects of the aging process, including cellular senescence, chronic inflammation, and cognitive decline. Genetic variations in the coding region of humanin and MOTS-c that are associated with age-related diseases are also reviewed, with particular emphasis placed on how mitochondrial variants might, in turn, regulate MDP expression and age-related phenotypes. Taken together, these observations suggest that mitochondrial-derived peptides influence or regulate a number of key aspects of aging and that strategies directed at increasing mitochondrial-derived peptide levels might have broad beneficial effects.


Staging and treatment outcomes in oropharyngeal squamous cell carcinoma: a single-centre UK cohort.
The 8th edition of the UICC TNM (UICC 8) staging rules for oropharyngeal squamous cell carcinoma (OPSCC) acknowledges dichotomous disease biology based on the human papillomavirus (HPV) tumour status. This retrospective study was undertaken to validate those staging rules in a single UK treatment centre. Given a recent resurgence of interest in primary surgery for OPSCC, a secondary objective was to identify subsets of patients who might benefit. Patients presenting with OPSCC between 2010 and 2017 to the South Glasgow head and neck multidisciplinary team were identified from a prospective database. Only patients managed with curative intent were included (n=272). Stage group allocation according to the UICC 8 resulted in appropriate hazard discrimination, in contradistinction to the UICC 7 staging rules. Locally advanced (cT3-4) disease had a relatively poor prognosis irrespective of HPV status. No clear benefit for primary surgery in any subgroup was demonstrated. A dichotomous disease biology based on the HPV status of tumour is confirmed in this cohort. Patients with HPV-positive T1 and T2 primary tumours have an excellent prognosis when treated with non-surgical treatment regimens. The use of surgery as the primary management for categories of patients presenting with OPSCC should be in the context of clinical trials.


Improved resolution with one-dimensional polyacrylamide gel electrophoresis: myofibrillar proteins from typed single fibers of human muscle.
Standard procedures for one-dimensional discontinuous sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis and silver staining were modified to give more effective separation and an improved resolution of human skeletal muscle proteins. In this system, an electrophoresis buffer composed of 100 mM L-isoleucine, 25 mM Tris base, and 0.1% SDS was used. The separating gel consisted of 16% acrylamide with N,N'-methylenebisacrylamide as a crosslinker (1:23), 0.4% SDS, 1.5 M Tris-HCl, pH 8.8. By the present procedure, the slow and the fast forms of myosin light chains (LCs, LCf) and other contractile proteins from human muscle could be better separated. The silver stain is based on a combination of methods previously described. The modified method requires a small fragment of a single fiber to observe as few as 10 ng of myofibrillar muscle proteins. The described simplifications made it possible to assay and compare up to 40 single fibers in the same electrophoretic run. Improved separation of other proteins migrating at basic pH could be achieved by a similar approach.


Discovery and optimization of a new class of potent and non-chiral indole-3-carboxamide-based renin inhibitors.
Selective inhibition of the aspartyl protease renin has gained attraction as an interesting approach to control hypertension and associated cardiovascular risk factors given its unique position in the renin-angiotensin system. Using a combination of high-throughput screening, parallel synthesis, X-ray crystallography and structure-based design, we identified and optimized a novel series of potent and non-chiral indole-3-carboxamides with remarkable potency for renin. The most potent compound 5k displays an IC(50) value of 2nM.


Needlestick and occupational exposure to infections: a compendium of current guidelines.
Needlestick and occupational exposure to infections is a constant threat in dental practice. Many blood-borne infections, including human immunodeficiency virus (HIV) infection, hepatitis B and hepatitis C, may be contracted through this route. We provide here a useful compendium for dental practitioners on current guidelines available to obviate such threats, as well as a simple flowchart on prophylactic measures that could be taken after an accidental exposure.


[Medical-work capacity examination of patients with chronic empyema of the pleura after pulmonectomy].
Treatment and analysis of immediate results were described in 269 patients with chronic empyema of the pleura as well as their long-term results in 207 of them. Under consideration were main criteria of the examination of labor capacity in such patients. It was shown that the establishment of the phase of "compensation at the limit" (IIa degree of pulmonary insufficiency) and subcompensation (IIb degree of pulmonary insufficiency) allowed more exact evaluation of the degree of compensatory processes of respiratory organs in patients after operation and the degree of loss of their working capacity.


Quantitative Anterior Enlargement of the Spinal Canal by Anterior Controllable Antedisplacement and Fusion for the Treatment of Cervical Ossification of the Posterior Longitudinal Ligament with Myelopathy.
This retrospective study aimed to investigate the effect of quantitative enlargement of spinal canal by anterior controllable antedisplacement and fusion (ACAF) for cervical ossification of the posterior longitudinal ligament (OPLL). Forty-three patients with OPLL who underwent ACAF were enrolled. According to the use of a curvature ruler (CR), patients were divided into group A (CR used, n = 21) and group B (CR not used, n = 22). The average follow-up was 9.5 months. The occupation rate (OR) of the spinal canal and the curvature of the cervical plate were recorded. The Japanese Orthopedic Association (JOA) scores were analyzed, and the recovery rate (RR) was calculated. Surgical complications were also investigated. The OR of the spinal canal in group A decreased from 66.7% ± 12.8% to 19.1% ± 10.9% after surgery (P < 0.05). In group B, the preoperative and postoperative OR was 63.9% ± 11.7% and 21.2% ± 8.7%, respectively (P < 0.05). Patients in group A had higher agreement of the curvature of the cervical plate between preoperative planning and postoperative measurement. The RR of JOA scores in group A was 73.7% ± 19.7%, higher than in group B (70.9% ± 7.3%, P > 0.05). Further comparison between the 2 groups, excluding those patients with OR <50%, showed that both JOA score and RR in group A were higher than in group B at the final follow-up (P < 0.05). The quantitative enlargement of the spinal canal by ACAF may provide a positive and favorable effect on enlarging the spinal canal and achieving better neurologic recovery for the treatment of cervical OPLL with myelopathy. CR can facilitate the achievement of better and more quantitative spinal canal enlargement.


A double-blind comparison of felodipine and hydrochlorothiazide added to metoprolol to control hypertension.
Seventy-six uncomplicated hypertensive patients treated in General Practice, whose seated diastolic blood pressure (Phase V) (dBP) remained greater than or equal to 95 mmHg after a minimum of 4 weeks treatment with metoprolol 50 mg b.i.d. as antihypertensive monotherapy, were randomized to receive the selective 'calcium antagonist' felodipine 5 mg b.i.d. or hydrochlorothiazide 12.5 mg b.i.d. in addition to metoprolol 50 mg b.i.d. The trial duration was 8 weeks, the dose of the felodipine or hydrochlorothiazide being doubled after 4 weeks if 'control' of BP (dBP less than 90 mmHg) was not achieved on the initial doses. Over the trial period of 8 weeks, felodipine reduced dBP from 102 to 85 mmHg and hydrochlorothiazide from 101 to 91 mmHg; the dBP reduction in the felodipine group was greater than that in the hydrochlorothiazide group (17 vs 9 mmHg) and the attained dBP lower in the felodipine group. About half of the patients in each group required the higher dose. Both regimes were effective and well tolerated. In the dosages used, felodipine was a slightly more effective antihypertensive drug than hydrochlorothiazide when added to metoprolol. There was no apparent difference in the tolerability of the two regimes.


Low prevalence of cervical intraepithelial neoplasia among Egyptian females.
Analysis of 4458 patients evaluated by cytology at the Department of Obstetrics and Gynecology, Kasr El-Einy Hospital, Cairo University, during the years 1981 to 1985 revealed that only 1.07% of these women had abnormal cytology. The prevalence rate for cervical intraepithelial neoplasia (CIN) was remarkably low, corresponding to 3.59/1000 for CIN grade I, 2.28/1000 for CIN II, and 1.16/1000 for CIN III. The mean age for CIN was 44.23 years while that for cervical cancer was 54.32. This low prevalence rate of CIN among Egyptian females, together with the late onset of the disease in comparison with other populations, calls for further study of the epidemiologic characteristics of this low-risk community.


Congenital urinary tract obstruction.
Congenital bladder neck obstruction (or lower urinary tract obstruction [LUTO]) describes a heterogeneous group of congenital anomalies presenting with similar prenatal ultrasonographic findings of dilated posterior urethra, megacystis, hydronephrosis, oligohydramnios and often with associated renal dysplasia. Untreated LUTO has high rate of perinatal morbidity and mortality from associated pulmonary hypoplasia and early-onset renal failure in infancy. Ultrasonographic features and prospective fetal urinalysis may help in predicting the overall prognosis of congenital LUTO. Currently, fetal vesicoamniotic shunt (of various designs), and fetal cystoscopy and fulguration of the obstruction are potential prenatal interventions. Retrospective and prospective cohort studies and a relatively small randomized controlled trial have demonstrated these treatments may possibly improve perinatal survival. Despite this, concerns remain as to the high rates of renal impairment observed in paediatric survivors. A clinical prospective scoring/staging system may improve prenatal diagnostic criteria and case selection for fetal therapy.


Influence of age on the diagnostic accuracy of soluble biomarkers for tuberculous pleural effusion: a post hoc analysis.
Accurately diagnosing pleural effusion is a frequent and significant problem in clinical practice. Combining pleural biomarkers with patients' age may be a valuable method for diagnosing TPE. We sought to evaluate the influence of age on diagnostic values of pleural adenosine deaminase (ADA), interferon-gamma (IFN-γ), and interleukin 27 (IL-27) for tuberculous pleural effusion (TPE). Two hundred seventy-four consecutive adult patients with pleural effusion were selected from Beijing and Wuhan between January 1, 2014 and June 30, 2015, and their pleural fluid concentrations of ADA, IFN-γ, and IL-27 were tested. Biomarker performance was analyzed by standard receiver operating characteristic (ROC) curves according to different ages. Data from the Beijing cohort showed that ADA, IFN-γ, and IL-27 could all accurately diagnose TPE in young patients (≤ 40 years of age). With a cutoff of 21.4 U/L, the area under the curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of ADA for diagnosing TPE were 1.000 (95% confidence interval: 0.884-1.000), 100.0, 100.0%, 100.0, and 100.0, respectively. In older patients (> 40 years of age), IL-27 and IFN-γ were excellent biomarkers for discriminating TPE versus non-TPE cases. With a cutoff of 591.4 ng/L, the AUC, sensitivity, specificity, PPV, and NPV of IL-27 for diagnosing TPE were 0.976 (95% confidence interval: 0.932-0.995), 96.3, 99.0%, 96.3, and 99.0, respectively. Similar diagnostic accuracy among the three pleural biomarkers was validated in the Wuhan cohort. Among young patients, ADA is reliable for diagnosing TPE. Conversely, in older patients, IL-27 and IFN-γ are excellent biomarkers to differentiate TPE versus non-TPE cases.


Transmission characteristics of a Fabry-Perot etalon-microtoroid resonator coupled system.
The transmission spectra of a Fabry-Perot etalon coupled to a microtoroid resonator are studied theoretically and experimentally. The resonance line shapes depend strongly on the resonance wavelength detuning and coupling strength between the two resonators. A wide variety of line shapes, ranging from a single to triple peaks, symmetric to asymmetric Fano-like peaks, and notches were predicted and observed experimentally. The capability to modify the spectral line shapes by tuning the coupling between or losses of two resonators may find applications in optical filtering, switching, sensing, and dispersion engineering.


Drug repurposing in idiopathic pulmonary fibrosis filtered by a bioinformatics-derived composite score.
Idiopathic Pulmonary Fibrosis (IPF) is a rare disease of the respiratory system in which the lungs stiffen and get scarred, resulting in breathing weakness and eventually leading to death. Drug repurposing is a process that provides evidence for existing drugs that may also be effective in different diseases. In this study, we present a computational pipeline having as input a number of gene expression datasets from early and advanced stages of IPF and as output lists of repurposed drugs ranked with a novel composite score. We have devised and used a scoring formula in order to rank the repurposed drugs, consolidating the standard repurposing score with structural, functional and side effects' scores for each drug per stage of IPF. The whole pipeline involves the selection of proper gene expression datasets, data preprocessing and statistical analysis, selection of the most important genes related to the disease, analysis of biological pathways, investigation of related molecular mechanisms, identification of fibrosis-related microRNAs, drug repurposing, structural and literature-based analysis of the repurposed drugs.


A fully labelled image dataset of banana leaves deficient in nutrients.
Agriculture is the art and science of cultivating the soil, growing crops and raising livestock. Enhancing crop yield becomes essential to improve economy in agriculture sector. Crops need 16 essential nutrients in balanced factor for their proper growth. Deficiency among these essential nutrients causes stunted growth often leading to significant crop loss. Symptoms of nutrient deficiency in plants can be observed visually which needs to be diagnosed correctly to rectify the problem, so that plants can grow healthily, increasing its yield. Among various crops, banana is one of the staple foods for millions of people across country and world. They contain essential nutrients that can have a defending impact on health of the human beings. The year-round availability, affordability, varietal range, taste, nutritive of banana and medicinal value makes it the favorite fruit among all classes of people. In addition, it also has good export potential. Few of the symptoms due to nutrient's deficiency in banana leaves are like curling of leaves, appearance of yellow strips, yellowing of the leaves, bluish color of young leaves. Deficiency symptoms can be visualized prominently on the leaves of the plant. Further, Machine Learning models can be developed to detect nutrient deficiency in leaves and help farmers in taking relevant measures. Thus, a fully labelled dataset becomes essential to train and test these models to detect nutrient deficiency accurately. The dataset created consists of banana leaf images of various categories like Musa acuminata (Dwarf Cavendish), Robusta, Rasthali, Poovan, Monthan, Elakkibale. Images depict deficiency in eight class of nutrients: boron, calcium, iron, potassium, manganese, magnesium, sulphur and zinc. Table 1 summarizes the essential nutrients and their deficiency symptoms visible on the leaves. Dataset also contains images of healthy leaves. Machine Learning Models can be developed by researchers and students and train them by using the created banana dataset to obtain high accuracy.


Acute retinal necrosis following dexamethasone intravitreal implant (Ozurdex®) administration in an immunocompetent adult with a history of HSV encephalitis: a case report.
Dexamethasone intravitreal implants (0.7 mg) (Ozurdex®, Allergan Inc., Madison, NJ) are FDA approved for managing macular oedema (ME) of retinal vein occlusion (RVO). The major complications associated with intravitreal Ozurdex® implant include increased intraocular pressure and cataract progression. In regard to the occurrence of retinal complications, we report an unusual intravitreal Ozurdex® implantation-related acute retinal necrosis (ARN). A 45-year-old immunocompetent woman with a history of encephalitis presented with photophobia, redness, floaters, and rapidly decreased vision in her left eye. Three and six months ago, she received two doses of intravitreal Ozurdex® implant for ME of RVO. Clinical evaluation, including slit-lamp biomicroscopy, retinal photography, and fluorescein angiography, revealed anterior chamber cells, granulomatous keratic precipitates, cells in the vitreous, optic disc oedema, occlusive retinal vasculitis, scattered retinal haemorrhages, one quadrant of peripheral white areas with retinal necrosis, optic disc and vessels fluorescein staining, and retinal nonperfusion zones. All the above clinical manifestations showed an ARN. Herpes simplex virus was detected in the aqueous and vitreous humour by quantitative polymerase chain reaction testing. Intravenous acyclovir 500 mg tid for 7 days followed by oral valcyclovir was immediately performed for ARN. At 4 months, the patient's condition improved without retinal detachment, and the best-corrected visual acuity remained stable at 0.3. ARN might represent a risk of Ozurdex® administration.


Bilateral synchronous carcinoma breast- a rare case presentation.
Bilateral Breast Carcinoma (BBC) is a rare entity with incidence of synchronous carcinoma being 2-5% of all breast malignancies, which is much less than metachronous carcinoma. Synchronicity/ metachronicity are usually associated with local and lymphatic spread and with blood-borne spread to lungs, bones and liver. Moreover BBC are mostly lobular carcinomas but we report a rare case of Infiltrating Ductal Carcinoma (IDC) as the primary carcinoma and Lobular Carcinoma as the secondary. 56 year old female who presented with a Stage IIIB fungating growth around 10x8cm in the lower inner, lower outer and upper outer quadrant of right breast since 6 months and a StageIIA 4x4cm tumour felt in the left breast in the upper inner and lower outer quadrant. Wedge biopsy of the right breast fungating mass showed Ductal Carcinoma and FNAC of the left breast lump suggested Lobular carcinoma which was confirmed on Histopathology after surgery. Patient was subjected to Hormonal therapy (Tab Tamoxifen), chemotherapy (Cyclophosphamide, 5 FU, and Doxorubicin) followed by Radiotherapy. Patient recovered well and shows no recurrence or signs of metastasis in the 8 months of follow up. Different histological subtypes with different grades of tumour in both breasts suggested two different synchronous primary tumours. Early detection of the contralateral tumour is of utmost importance emphasising the significance of breast self-examination. Screening tools like MRI have a greater sensitivity compared to Mammography. There are no clear treatment guidelines for bilateral breast cancer. Patients are often treated with bilateral mastectomy, with breast conservative surgery having unclear importance. Meticulous diagnosis and appropriate management help to improve the longitivity with an improved quality of life.


Testing rate and cementation seating load effects on resin-strengthening of a dental porcelain analogue.
To determine the resin-strengthening dependence of a soda-lime-glass analogue for dental porcelain as a function of biaxial flexure strength (BFS), test crosshead rate and cementation seating load. Disc-shaped soda-lime glass specimens were divided into twelve groups (n=24), alumina particle air abraded and hydrofluoric acid-etched. Specimens (Groups A-D) were stored in a desiccator prior to testing at crosshead rates of 0.01, 0.1, 1 and 10mm/min, respectively. The remaining specimens were silane treated, Rely-X Veneer resin-coated with a seating load of 5N (Groups E-H) and 30N (Groups I-L) prior to light irradiation at 480±20mW/cm(2), 24h dry storage and BFS testing at 0.01, 0.1, 1 and 10mm/min, respectively. A linear logarithmic regression curve was fit to the raw data to elucidate static fatigue effects of the soda-lime-glass. Analysis of group means was performed utilising a general linear model univariate analysis and post hoc all paired Tukey tests (P<0.05). The linear logarithmic regression curve demonstrated the static fatigue effects of the soda-lime-glass analogue. Rely-X Veneer resin-coating (Groups E-L) resulted in significant increases in the mean BFS data for all crosshead rates examined (all P<0.001). However, the pattern of rate dependence effects on resin-cementation deviated from the log relationship observed with the uncoated controls. This study further highlights that when slow crack growth is simulated during testing, valuable insights into the significant modification of a hereto well described phenomenon such as resin-strengthening mediated by the resin-ceramic hybrid layer is provided.


Use of DNA polymorphisms and the polymerase chain reaction to examine the survival of a human limbal stem cell allograft.
The extent to which limbal epithelial stem cell allografts will repopulate the human corneal ocular surface, and the time frame over which such cells survive, are uncertain. We investigated the survival of donor-derived epithelial cells after limbal stem cell allotransplantation in a patient with bilateral limbal stem cell failure by using short tandem-repeat DNA polymorphisms to distinguish donor and recipient cells. Epithelial cells were harvested by impression cytology from the grafted eye before and at various times after transplantation. DNA was extracted and amplified by the polymerase chain reaction at an informative locus, D8S264. Cells of donor genotype were present over the grafted areas at the time of surgery but were not detected in the central cornea until 12 weeks postoperatively, indicating that repopulation of the epithelial surface from transplanted limbal stem cells took considerable time. However, by the 20th postoperative week, only recipient-type cells were detected in the grafted eye, despite systemic immunosuppression of the recipient with azathioprine and cyclosporine. Discrimination between donor and recipient cells on the ocular surface after limbal allotransplantation was possible using genotypic variation at DNA polymorphic sites (microsatellites). Long-term survival of donor cells after limbal transplantation did not occur in this patient. Detection of DNA polymorphisms amplified by the polymerase chain reaction is a simple, rapid, and noninvasive method of following the course of transplanted cells at the ocular surface.


Age-dependent and tissue-specific structural changes in the C57BL/6J mouse genome.
We tested the hypothesis that structural changes in the genome parallel age- and organ-specific phenotypes in conjunction with the differential transposition activities of retroelements. The genomes of the liver from C57BL/6J mice were larger than other organs, coinciding with an increase in genomic copies of certain retroelements. In addition, there were differential increments in the genome size of the liver with increasing age, which peaked at 5 weeks. The findings that the genome structure of an individual is variable depending on age and organ type in association with the transposition of retroelements may have broad implications in understanding biologic phenomena.


Large area of the false lumen favors secondary dilatation of the aorta after acute type A aortic dissection.
Since 1994 patients with acute aortic dissection type A (AADA) are followed-up in our outpatient clinic. Early diagnosis of secondary dilatation of the diseased aorta is crucial to reduce late mortality in these patients. Aim of the present study is to asses the impact of a large volume in the false lumen of the diseased downstream aorta on secondary dilatation. 134 patients of 264 patients who underwent surgery for AADA (between January 1994 and June 2003) are followed-up at our outpatient clinic since 1994. 84 patients (62.7%) fulfilled the inclusion criteria. Areas of the true and the false lumens of the aorta were analyzed and a logistic regression was calculated at 5 levels of the aorta for each patient. Patients were divided in 3 groups: group 1 included 34 patients (40.5%) without progression, group 2 had 34 patients (40.5%) with slight progression, and group 3 had 16 patients (19.0%) with important progression, requiring surgery in all patients. In 87.5% of the patients the area of the original lumen was <0% in group 3, compared with 11.8% in group 2 and 8.8% in group 1 in relation to the total area of the aorta 6 months after surgery (P<0.001). A large false lumen, with an area of the true lumen <30% 6 months after surgery, is the strongest predictor for secondary dilatation of the diseased downstream aorta.


RAxML Grove: an empirical phylogenetic tree database.
The assessment of novel phylogenetic models and inference methods is routinely being conducted via experiments on simulated as well as empirical data. When generating synthetic data it is often unclear how to set simulation parameters for the models and generate trees that appropriately reflect empirical model parameter distributions and tree shapes. As a solution, we present and make available a new database called 'RAxML Grove' currently comprising more than 60 000 inferred trees and respective model parameter estimates from fully anonymized empirical datasets that were analyzed using RAxML and RAxML-NG on two web servers. We also describe and make available two simple applications of RAxML Grove to exemplify its usage and highlight its utility for designing realistic simulation studies and analyzing empirical model parameter and tree shape distributions. RAxML Grove is freely available at https://github.com/angtft/RAxMLGrove. Supplementary data are available at Bioinformatics online.


[Effect of vagotomy with antrumectomy on very high acid production in duodenal ulcer patients].
In patients with hyperacidic duodenal ulcer the hyperproduction of hydrochloric acid was shown to occur both during the nervous-reflectory and humoral phases of secretion. Vagotomy with antrumectomy is considered to be the most effective method in such patients, since it inhibits both the I and II phases of the acid gastric secretion.


A pilot study: sequential gemcitabine/cisplatin and icotinib as induction therapy for stage IIB to IIIA non-small-cell lung adenocarcinoma.
A phase II clinical trial previously evaluated the sequential administration of erlotinib after chemotherapy for advanced non-small-cell lung cancer (NSCLC). This current pilot study assessed the feasibility of sequential induction therapy in patients with stage IIB to IIIA NSCLC adenocarcinoma. Patients received gemcitabine 1,250 mg/m(2) on days 1 and 8 and cisplatin 75 mg/m(2) on day 1, followed by oral icotinib (125 mg, three times a day) on days 15 to 28. A repeat computed tomography(CT) scan evaluated the response to the induction treatment after two 4-week cycles and eligible patients underwent surgical resection. The primary objective was to assess the objective response rate (ORR), while EGFR and KRAS mutations and mRNA and protein expression levels of ERCC1 and RRM1 were analyzed in tumor tissues and blood samples. Eleven patients, most with stage IIIA disease, completed preoperative treatment. Five patients achieved partial response according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria (ORR = 45%) and six patients underwent resection. Common toxicities included neutropenia, alanine transaminase (ALT) elevation, fatigue, dry skin, rash, nausea, alopecia and anorexia. No serious complications were recorded perioperatively. Three patients had exon 19 deletions and those with EGFR mutations were more likely to achieve a clinical response (P= 0.083). Furthermore, most cases who achieved a clinical response had low levels of ERCC1 expression and high levels of RRM1. Two cycles of sequentially administered gemcitabine/cisplatin with icotinib as an induction treatment is a feasible and efficacious approach for stage IIB to IIIA NSCLC adenocarcinoma, which provides evidence for the further investigation of these chemotherapeutic and molecularly targeted therapies.


Hospital variation in treatment patterns and oncological outcomes for patients with muscle-invasive and metastatic bladder cancer in the Netherlands.
Population-based studies on treatment patterns in oncology and corresponding clinical outcomes can help identify strategies towards optimal value for patients. This study was performed to describe the variation in treatment patterns and major oncological outcomes for muscle-invasive or metastatic bladder cancer (MIBC/mBC) patients in the Netherlands. Patients diagnosed with cT2-4aN0-3M0-1 disease between 2008 and 2016 in seven large teaching hospitals in the Netherlands were included. Baseline characteristics, disease stage, intended and definitive treatment, and oncological outcomes were collected. Patients were categorized based on cTNM-stage: (1) cT2-4aN0M0, (2) cT2-4aN1-3M0 and (3) cT4b and/or M1. The total study population comprised 1853 patients, of which 1303 patients were diagnosed with cT2-4aN0M0 disease. Overall, curative treatment was intended in 81% (range 74-85%, P value = 0.132). Radical cystectomy (RC) and curative radiotherapy (RTx) ranged between hospitals from 42 to 66% and 13 to 27%, respectively (P value < 0.001). For 334 patients staged cT4b and/or M1, frequencies for palliative therapy and best supportive care (no anti-cancer therapy) ranged between hospitals from 20 to 54% and 44 to 71%, respectively (P value < 0.001). There was no association between hospital site and overall survival (OS) in a univariable and multivariable Cox regression for survival analysis (after adjusting for age and cT-stage), for all three cTNM-groups. Neoadjuvant or induction chemotherapy (NAIC) utilization rates before RC ranged from 8 to 38% (P value < 0.001). There is large inter-hospital variation in treatment intent in MIBC/mBC patients. This variation does not seem to translate to differences in overall survival rates. There is an ongoing trend of increased use of RC. Utilisation of NAIC is relatively low considering European guideline recommendations.


Comparison of Modified Manual Acid-Phenol Chloroform Method and Commercial RNA Extraction Kits for Resource Limited Laboratories.
In a comparative experimental cross-sectional study, RNA was extracted from oral swabs and blood samples from 25 healthy individuals at the Department of Molecular Medicine, KNUST. RNA was extracted by the manual AGPC extraction method and commercial RNA extraction kits. The quantity (ng/μl) and purities (260/280 nm) of the extracted RNA were measured spectrophotometrically using the IMPLEN NanoPhotometer® N60. The presence of RNA in the extracts was confirmed using 2% agarose gel electrophoresis. Statistical analyses were conducted using R language. The yield of RNA extracted from blood and oral swab samples using modified AGPC was significantly higher compared to the commercial methods (p < 0.0001). However, the purity of RNA extracted by the manual AGPC method from blood was significantly lower than the commercial methods (p < 0.0001). Moreover, the purity from oral swabs using the manual AGPC method was significantly lower compared to QIAamp (p < 0.0001) and the OxGEn kits method (p < 0.001). The modified manual AGPC method has a very high yield of RNA extracts using blood samples, which could serve as an alternate cost-effective method for RNA extraction in resource-limited laboratories; however, its purity may not be suitable for downstream processes. Moreover, the manual AGPC method may not be suitable for extracting RNA from oral swab samples. Future investigation is needed to improve the purity of the manual AGPC RNA extraction method and also confirmation of the obtained results by PCR amplification and RNA purity verification by sequencing.


Determining the core competencies for international postgraduate nursing students in internship programs: A delphi study.
To determine the core competencies of clinical internships for international postgraduate nursing students undertaking a two-year professional program in China. Clinical internship is an important part of nursing education and is the cornerstone for the future training of nursing professionals. However, in terms of providing a basis for the training and assessment of international postgraduate nursing students undertaking a two-year professional program in China, their core competencies of clinical internships have not yet been sufficiently determined. Focus group interviews and a two-round Delphi method were conducted. The preliminary list of core competencies was determined based on a scoping review and focus group interviews. Subsequently, experts provided suggestions for modifications to the core competencies in two rounds of the Delphi survey. The response rate (RR), composite reliability (Cr), coefficient of variation and Kendall coefficient of indices were calculated. Twenty experts completed two rounds of Delphi expert consultation and reached consensus on five first-level indices and 13 s-level indices with 27 connotations. The RR values for the two rounds of consultation were 100 %, the Cr values were 0.853 and 0.873 and the Kendall coordination coefficients were 0.134-0.250 (p < 0.05). The core competencies identified in this research can provide a basis for further training international postgraduate nursing students undertaking a two-year professional program in China through internship programs. This research also provides a reference for effectively evaluating and improving clinical programs.


Endothelin-1 Gene Polymorphisms rs5370, rs1476046, and rs3087459 are not Associated with Diabetic Nephropathy in Caucasians with Type 2 Diabetes Mellitus.
Diabetic nephropathy (DN) is a major microvascular complication of type 2 diabetes mellitus (T2DM). Several lines of evidence implicate the endothelin (ET) system in the pathophysiology of DN. The aim of the present study was to analyze if genetic polymorphisms of the ET-1 (EDN1) gene affect susceptibility to DN in Caucasians with T2DM. The study population consisted of 651 Caucasian subjects with T2DM of more than 10 years' duration: 276 patients with DN (cases) and 375 patients without evidence of DN (controls). Polymorphisms in ET-1 (EDN1) gene, rs5370, rs1476046, and rs3087459, were studied. Genotype distributions of the studied polymorphisms showed no significant difference between cases and controls. We provide evidence that the rs5370, rs1476046, and rs3087459 polymorphisms of EDN1 gene are not risk factors for DN in Caucasians with T2DM.


Purification, crystallization and preliminary X-ray diffraction analysis of the CBS-domain pair from the Methanococcus jannaschii protein MJ0100.
CBS domains are small protein motifs consisting of a three-stranded beta-sheet and two alpha-helices that are present in proteins of all kingdoms of life and in proteins with completely different functions. Several genetic diseases in humans have been associated with mutations in their sequence, which has made them promising targets for rational drug design. The C-terminal domain of the Methanococcus jannaschii protein MJ0100 includes a CBS-domain pair and has been overexpressed, purified and crystallized. Crystals of selenomethionine-substituted (SeMet) protein were also grown. The space group of both the native and SeMet crystals was determined to be orthorhombic P2(1)2(1)2(1), with unit-cell parameters a = 80.9, b = 119.5, c = 173.3 A. Preliminary analysis of the X-ray data indicated that there were eight molecules per asymmetric unit in both cases.


Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) in a Greek family.
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an adult-onset inherited disease, characterised by recurrent strokes, migraine and cognitive impairment. We present the first Greek family with CADASIL, caused by the R153C mutation at exon 4 of the Notch3 gene. A member of this family carrying this mutation was also found to be heterozygotic for the MTHFR mutation, factor V Leiden mutation and had low serum levels of antithrombin III, thus resulting in the appearance of recurrent strokes and thrombotic episodes since his early adulthood. The co-existence of these thrombophilic disorders with CADASIL in a single person poses serious therapeutic dilemmas, as the administration of anticoagulant agents may correlate with increased risk of potentially fatal intracerebral haemorrhage.


Computer-assisted alignment system for tibial component placement in total knee replacement: a radiological study.
In total knee replacement (TKR), regarding tibial component positioning, almost all implants offer both an intramedullary and an extramedullary alignment guide, leaving it up to the surgeon which guide to use. However, early failure in TKR can be caused by incorrect positioning or orientation with poor limb alignment. Recently computer-based alignment systems have been developed to help the surgeon to overcome these complications. The Authors retrospectively analysed their experience using a computer-based CT-free alignment system. They assessed the radiological alignment of the tibial components in 38 computer-assisted TKR 6 months after surgery. The frontal tibial component angle (FTC) and the sagittal orientation of the tibial component (slope) were evaluated 6 months after the operation. The results were compared to those achieved with traditional alignment systems. The surgical time was statistically longer in the computer-assisted group but in this group all the tibial components were aligned within 4 degrees of all the ideal measurements in both frontal and sagittal planes.


Corrigendum.
Mr. Richard J. George was misidentified as "Richard G. George" as the co-author of the work entitled, "Characterization of Archaeological Sediments Using Fourier Transform Infrared (FT-IR) and Portable X-ray Fluorescence (pXRF): An Application to Formative Period Pyro-Industrial Sites in Pacific Coastal Southern Chiapas, Mexico", by Hector Neff, Scott J. Bigney, Sachiko Sakai, Paul R. Burger, Timothy Garfin, Richard J. George, Brendan J. Culleton, and Douglas J. Kennett, [Applied Spectroscopy, January 2016, vol. 70(01): 110-127. doi: 10.1177/0003702815617124]. We apologize for the error.


Practical way to apply fourth-generation assessment tools integrated into creating meaningful learning experiences in biology at high school.
The learning process for a Biology topic regarding organisms and animal kingdom diversity was investigated through an innovative Interactive Didactic Sequence (IDS) which integrated the idea of "concept maps" with the Hermeneutic-Dialectic Circle (HDC). HDC is a tool for data collection and a reference for pluralist-constructivist thinking, considered a form of fourth-generation evaluation. Hofstede's cultural dimensions were also integrated into the investigation in order to facilitate mediation in an evaluative context. Students' performances (N = 25) from a São Paulo-Brazil public school were statistically evaluated. Their cultural profile was determined via the Hofstede Value Survey Model 1994 questionnaire. The elaborative process of arranging concept maps was individual (CM-individual) and integrated with HDC in groups (CM-HDC). Concept map assessment methods were based off existing literature. An improvement in students' performances (p < 0.05) that presented concept maps integrated to HDC in a more complex structure when compared to individually-built maps was observed. Employment of HDC helped form motivational/interactive dialogues between students and teachers, which, in turn, assisted in achieving greater learning through the use of concept maps. The application of the fourth-generation evaluation was improved via knowledge regarding students' cultural profiles.


Greenspace and children's lung function in China: A cross-sectional study between 2013 and 2015.
This study aims to investigate how surrounding greenspace density and proximity were associated with children's lung function. Between 2013 and 2015, spirometry and a parental survey were performed with children from four primary schools in two Chinese cities. Forced expiratory volume in 1 s (FEV1, L), forced vital capacity (FVC, L), peak expiratory flow rate (PEF, L/s), and forced expiratory flow at 25 % (FEF25, L/s) and 75 % (FEF75, L/s) of FVC were measured. Outdoor surrounding greenspace index incorporated residential, school and commuting greenness and was weighted using assumed daytime hours spent at home and school. Residential proximity to greenspace index was defined as walking distance to nearest park. A total of 913 children (48.7 % female) were included. Overall, an interquartile range (IQR) increase in outdoor surrounding greenspace was associated with decreased FVC (0.06 L, 95%CI 0.01-0.11), but increased FEV1/FVC (2.03, 1.13-3.04), PEF (0.26 L/s, 0.13-0.39), and FEF25 (0.30 L/s, 0.17-0.42). Residential proximity to greenspace was associated with increased FEV1 (0.05 L, 0.02-0.08) and FVC (0.04 L, 0.01-0.07) per IQR decrease in distance. Protective effect was significant for children whose parents were less educated and those living in higher road density areas, though interactions were not significant. Structural equation modeling showed that higher level of surrounding greenspace was associated with lower ambient air pollution and in turn with better lung function. Greenspace density and proximity could influence children's lung function differently.


Expression, purification, and characterization of recombinant human L-chain ferritin.
Ferritins form nanocage architectures and demonstrate their potential to serve as functional nanomaterials with potential applications in medical imaging and therapy. In our study, the cDNA of human L-chain ferritin was cloned into plasmid pET-28a for its overexpression in Escherichia coli. However, the recombinant human L-chain ferritin (rLF) was prone to form inclusion bodies. Molecular chaperones were co-expressed with rLF to facilitate its correct folding. Our results showed that the solubility of rLF was increased about 3-fold in the presence of molecular chaperones, including GroEL, GroES and trigger factor. Taking advantage of its N-terminal His-tag, rLF was then purified with Ni-affinity chromatography. With a yield of 10 mg/L from bacterial culture, the purified rLF was analyzed by circular dichroism spectrometry for its secondary structure. Furthermore, the rLF nanocages were characterized using dynamic light scattering and transmission electron microscopy.


Investigation of pollution characteristics of polychlorinated biphenyls in the typical drinking water sources in Jiangsu Province, China.
Concentration and composition of polychlorinated biphenyls (PCBs) in the typical drinking water sources in Jiangsu Province were studied by scene investigation and physical and chemical analyses as well. Total amount of PCBs in some surface water and surface microlayers exceeded the standard (20 ng/l) in the "Environmental Quality Standard of Surface Water". There were less PCBs in suspended substances and bottom mud. It reflected that there was less PCB pollution in drinking water sources in Jiangsu Province for quite a long period. The main kind of PCBs in the typical drinking water sources was dichlorobiphenyl. Monochlorobiphenyl and trichlorobiphenyl ranked next to dichlorobiphenyl. In the study of PCB distribution in drinking water sources, it was found that the concentration of PCBs in surface microlayer was higher than that in deep water. The concentration of PCBs along the Yangtze River bank was more than that in the middle of Yangtze River. PCBs in the typical drinking water sources mostly came from by-products in industrial production.


A safe, effective, and facility compatible cleaning in place procedure for affinity resin in large-scale monoclonal antibody purification.
Cleaning-in-place (CIP) for column chromatography plays an important role in therapeutic protein production. A robust and efficient CIP procedure ensures product quality, improves column life time and reduces the cost of the purification processes, particularly for those using expensive affinity resins, such as MabSelect protein A resin. Cleaning efficiency, resin compatibility, and facility compatibility are the three major aspects to consider in CIP process design. Cleaning MabSelect resin with 50mM sodium hydroxide (NaOH) along with 1M sodium chloride is one of the most popular cleaning procedures used in biopharmaceutical industries. However, high concentration sodium chloride is a leading cause of corrosion in the stainless steel containers used in large scale manufacture. Corroded containers may potentially introduce metal contaminants into purified drug products. Therefore, it is challenging to apply this cleaning procedure into commercial manufacturing due to facility compatibility and drug safety concerns. This paper reports a safe, effective and environmental and facility-friendly cleaning procedure that is suitable for large scale affinity chromatography. An alternative salt (sodium sulfate) is used to prevent the stainless steel corrosion caused by sodium chloride. Sodium hydroxide and salt concentrations were optimized using a high throughput screening approach to achieve the best combination of facility compatibility, cleaning efficiency and resin stability. Additionally, benzyl alcohol is applied to achieve more effective microbial control. Based on the findings, the recommended optimum cleaning strategy is cleaning MabSelect resin with 25 mM NaOH, 0.25 M Na2SO4 and 1% benzyl alcohol solution every cycle, followed by a more stringent cleaning using 50 mM NaOH with 0.25 M Na2SO4 and 1% benzyl alcohol at the end of each manufacturing campaign. A resin life cycle study using the MabSelect affinity resin demonstrates that the new cleaning strategy prolongs resin life time and consistently delivers high purity drug products.


Persistent post-traumatic pseudosheath formation secondary to a movable organized blood clot.
Pseudosheath formation secondary to post-traumatic hematoma is described in a patient following blunt trauma to the lateral thigh. The theory of its formation and progression is discussed.


Helicobacter pylori infection produces reversible glycosylation changes to gastric mucins.
The protective ability of gastric mucins may depend largely on their oligosaccharide chains. We evaluated the effects of H. pylori infection on the glycosylation of gastric mucins. Gastric biopsy specimens from 20 H. pylori-infected patients before and after cure of the H. pylori infection and 8 normal uninfected volunteers were examined by immunostaining for simple mucin-type glycoproteins and blood-group-related antigens bearing type 1 chain backbone. The immunoreactivity in different gastric compartments was evaluated. Simple mucin-type glycoproteins and blood-group-related antigens were expressed in surface mucous cells. Simple mucin-type glycoproteins showed antrum-predominant expression in normal volunteers and were found in significantly fewer surface mucous cells in infected patients than in normal volunteers; their expression was restored after eradication of H. pylori. Sialyl Lewis(a) and Lewis(b) were expressed in fewer surface mucous cells after than before eradication. The patterns of glycosylation of gastric mucins vary in different gastric compartments and are reversibly altered by H. pylori infection. These alterations may affect the protective functions of gastric mucins.


Genome aliquoting revisited.
We prove that the genome aliquoting problem, the problem of finding a recent polyploid ancestor of a genome, with breakpoint distance can be solved in polynomial time. We propose an aliquoting algorithm that is a 2-approximation for the genome aliquoting problem with double cut and join distance, improving upon the previous best solution to this problem, Feijão and Meidanis' 4-approximation algorithm.


Controversies in pediatric anesthesia: sevoflurane and fluid management.
To explore the interrelationships among the pharmacokinetics of sevoflurane, epileptiform electroencephalographic (EEG) activity and awareness in children. To also describe the revised perioperative fluid management strategy espoused by Holliday and Segar and noninvasive measures that may predict who will respond positively to fluid loading. The depth of anesthesia during the early washin period with sevoflurane 8% is one-third less than during halothane. Eight percent sevoflurane rarely causes clinical seizures; more commonly, it causes epileptiform EEG activity that only weakly portends seizure activity. When preceded by nitrous oxide, midazolam or normocapnia, the risk of inducing epileptiform activity during spontaneous respiration is exceedingly small. Decreasing the inspired concentration of sevoflurane upon loss of the eyelash reflex to prevent epileptiform activity has not been shown to reduce the risk of clinical seizures, but more importantly, it may increase the risk of awareness if the child is stimulated. Isotonic intravenous solutions should be infused in volumes of 20-40 ml/kg over 2-4 h in children undergoing elective surgery. Postoperatively, these infusions may be continued at rates of 2/1/0.5 ml/kg/h; serum sodium concentration should be measured periodically. Noninvasive measures currently do not reliably identify those children who will respond positively to fluid boluses. Sevoflurane is a well tolerated induction agent that rarely causes seizures in children, but may cause awareness if the inspired concentration is prematurely reduced. Perioperative isotonic fluids should be infused at 20-40 ml/kg over 2-4 h during elective surgery. Noninvasive metrics do not predict a child's responsiveness to fluid loading.


[Disciform syndrome secondary to focal choroiditis in the macular region (author's transl)].
In 10 patients with an average age 44 years there developed from focal choroiditis in the macular region a disciform syndrome, clinically resembling the senile macular degeneration and with a poor prognosis.


Predation by non-bioluminescent firefly larvae on a tepui-summit endemic toad.
Tepuis are Precambrian sandstone tabletop mountains in South America that can reach up to ∼3,000 m in elevation. Their highest summits are both physiographically and ecologically isolated from the surrounding upland savannah and lush tropical rainforest, and they face particularly hostile, challenging environmental conditions [1,2] (Figure 1A). Taxa thriving on high tepui summits must adapt to resource-limited and highly competitive ecosystems. The toad genus Oreophrynella is exclusively found on tepui slopes and summits [3] and is particularly well-adapted to the tepui top environment. We here report on an unanticipated and possibly large-scale predation on this endemic toad by non-bioluminescent firefly larvae.


An epigenomic mechanism in retinoblastoma: the end of the story?
The role that retinoblastoma has played in our understanding of cancer biology could hardly have been imagined 40 years ago when this disease was a rare curiosity, of interest primarily because of its variable laterality, occasional dominant inheritance, frequent lethality and embyronal origin. The discovery of its cause (biallelic loss of RB1) did not offer insight to improved management. However, the recent discovery of aberrant expression of the gene encoding spleen tyrosine kinase (SYK) subsequent to widespread methylation abnormalities in retinoblastoma suggests a potential new therapy for the disease. There is more to the story, however.


Prospective Assessment of Scoliosis-Related Anxiety and Impression of Trunk Deformity in Female Adolescents Under Brace Treatment.
The aim of this study is to make a prospective analysis of changes in anxiety levels and determining their associations with a longitudinal subjective assessment of trunk deformity in adolescent females with scoliosis, in relation to clinical, radiological and brace-related data. The study design was comprised of three questionnaire assessments, with the second and third evaluations taking place 6 and 12 months after the beginning of the study, respectively. 36 AIS females treated conservatively were asked to fill in the Polish versions of the Spinal Appearance Questionnaire (SAQ-pl) and the trait version of the Spielberger's Anxiety Inventory for Children (STAIC-trait). High anxiety was indicated in 16.6, 8.3 and 8.3% during the 1st, 2nd and 3rd evaluations. Patients' results differ in regards to the Curve domain; the discrepancies concern the 2nd and 3rd and the 1st and 3rd evaluations (p = 0.028 and p = 0.003, respectively). The only association between STAIC-trait and SAQ-pl regards Trunk shift in the 1st evaluation (rs = 0.48). The logistic regression revealed that the duration of brace-wearing in months has a statistically significant (p = 0.021) influence on the probability of diagnosing patients' low anxiety levels in the 2nd assessment. Special attention should be paid to patients' emotional reactions later on as brace-wearing continues as well as to the results which support the point that patients' perceptions of spinal deformity do not deteriorate with treatment time. Clinicians need to be aware how patients' appearance-specific cognitions might be associated with levels of emotional distress and relate to clinical and radiological, scoliosis-related data.


Anti-HIV seropositivity was related to HBsAg seropositivity among injecting drug users in Taiwan.
In Taiwan, the number of new cases of human immunodeficiency virus (HIV) infection via drug injection has been increasing since 2003. Due to HIV and hepatitis B virus (HBV) having similar transmission routes, HBV and HIV infections among injecting drug users (IDUs) has become an important public health issue. The aim of this study was explore the prevalence of HBV infection among IDUs with and without HIV infection, and examine whether HIV infection is associated with HBV infection among IDUs in Southern Taiwan. We enrolled 566 IDUs, including 87 anti-HBV positive IDUs and 479 anti-HBV negative IDUs, and also analyzed the results of liver function tests, HBV DNA, anti-HIV, HIV RNA, and CD4 cell count. The results showed that the prevalence of HBV infection among IDUs was 15.4%. The prevalence of hepatitis B surface antigen (HBsAg) was higher among individuals born before 1985 (15.9% vs. 4.0%), but this was not significant. Anti-HIV seropositivity was related to HBsAg seropositivity [odds ratio (OR) = 2.47, 95% confidence interval = 1.26-4.82, p = 0.008). Anti-HCV and anti-HIV were risk factors for abnormal alanine aminotransferase (ALT; OR = 2.11, 95% confidence interval = 1.005-4.42, p = 0.048 and OR = 1.47, 95% confidence interval = 1.02-2.10, p = 0.04, respectively), and HBsAg was not a factor related to abnormal ALT. In conclusion, the prevalence of HBV infection was similar in the general population and in IDUs, and due to anti-HIV seropositivity being significantly related to HBsAg seropositivity, HBV infection among IDUs is still important. We suggest that for IDUs, HBsAg should be monitored closely.


Thyroperoxidase (TPO) immunostaining of the solitary cold thyroid nodule.
To evaluate the value of immunostaining using the monoclonal antibody (MoAB47) against thyroperoxidase (TPO) in distinguishing between benign and malignant tumour cells in fine needle aspiration cytology (FNAC) samples obtained from a solitary cold nodule of the thyroid gland for the purpose of strengthening the indication for thyroid surgery. A prospective, immunocytochemical study of FNACs taken from patients with solitary cold thyroid nodules who presented to Rigshospitalet, Copenhagen, Denmark, during the period April 1993 to May 1996. The first sample series was taken perioperatively in order to test the utility of the method. In the second part of the study samples were obtained preoperatively by ultrasonic guided aspiration. Tissue sections from the nodules obtained during a subsequent operation served as controls. One hundred and eighty-one patients, 150 women and 31 men, were studied. The age range was 14-89 years with a median age of 44 years. Fifty-seven patients were excluded from the study for various reasons leaving us with a total of 124 nodules from 124 patients for final evaluation. FNAC cells and corresponding nodular tissue were stained by immunocyto- and immuno-histochemistry using MoAb47 and by routine staining methods. Samples were considered benign if 80% or more of the epithelial-looking cells of both the FNACs and the histological tissue sections of the nodule were stained by TPO. Consequently, samples were considered malignant if more than 20% of the epithelial-looking cells failed to stain for TPO. Routinely stained tissue cells and sections served as diagnostic controls. A pattern with negative TPO staining was found in all lesions which, by conventional histological staining, were subsequently proven to be malignant. A universal and reliable, positive TPO staining pattern was found in all subsequently proven benign lesions, with the exception of one out of 26 follicular adenomas. This gave the method a sensitivity of 1.0 (negative TPO staining = malignancy in 27 out of 27) and a specificity of 0.99 (positive TPO staining = benign lesion, in 96 out of 97). Positive and negative predictive values were 0.96 and 1.00 respectively. Thyroperoxidase immunostaining of fine needle aspirates from solitary, scintigraphically cold nodules of the thyroid gland has proved to be an important and reliable diagnostic tool for distinguishing between benign and malignant nodules. Thus, patients might be spared further surgery if not otherwise indicated.


Ten years of integrated care for the older in France.
This paper analyzes progress made toward the integration of the French health care system for the older and chronically ill population. Over the last 10 years, the French health care system has been principally influenced by two competing linkage models that failed to integrate social and health care services: local information and coordination centers, governed by the social field, and the gerontological health networks governed by the health field. In response to this fragmentation, Homes for the Integration and Autonomy for Alzheimer patients (MAIAs) is currently being implemented at experimental sites in the French national Alzheimer plan, using an evidence-based model of integrated care. In addition, the state's reforms recently created regional health agencies (ARSs) by merging seven strategic institutions to manage the overall delivery of care. The French health care system is moving from a linkage-based model to a more integrated care system. We draw some early lessons from these changes, including the importance of national leadership and governance and a change management strategy that uses both top-down and bottom-up approaches to implement these reforms.


HN1 promotes tumor growth and metastasis of anaplastic thyroid carcinoma by interacting with STMN1.
Anaplastic thyroid carcinoma (ATC) is one of the most aggressive malignancies frequently associated with extrathyroidal extension and metastasis through pathways that remain unclear. Analysis of the cancer genome atlas (TCGA) database and an independent cohort showed that the expression of hematological and neurological expressed 1 (HN1) was higher in thyroid cancers than in normal tissues, and negatively correlated with progression-free survival. RT-PCR and immunohistochemistry revealed higher HN1 expression in ATC compared to healthy tissues and papillary thyroid carcinoma (PTC). HN1 knockdown attenuated migration and invasion of ATC cells, whereas HN1 overexpression increased migration and invasion of PTC cells. HN1 reduced the acetylation of α-tubulin and promoted progression through epithelial-mesenchymal transition of ATC cells and mouse xenografts. HN1 knockdown significantly attenuated TGF-β-induced mesenchymal phenotype, and inhibited tumor formation and growth of ATC xenografts in nude mice. Loss of STMN1 decreased the malignant potential of HN1, whereas HN1 knockdown in combination with STMN1 overexpression restored the aggressive properties of ATC cells. HN1 increased STMN1 mRNA expression, and prevented STMN1 ubiquitination and subsequent degradation. These results demonstrate that HN1 interacts with STMN1 and drives ATC aggressiveness.


Identification of HIV-1 reverse transcriptase dual inhibitors by a combined shape-, 2D-fingerprint- and pharmacophore-based virtual screening approach.
We report the first application of ligand-based virtual screening (VS) methods for discovering new compounds able to inhibit both human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT)-associated functions, DNA polymerase and ribonuclease H (RNase H) activities. The overall VS campaign consisted of two consecutive screening processes. In the first, the VS platform Rapid Overlay of Chemical Structures (ROCS) was used to perform in silico shape-based similarity screening on the NCI compounds database in which a hydrazone derivative, previously shown to inhibit the HIV-1 RT, was chosen. As a result, 34 hit molecules were selected and assayed on both RT-associated functions. In the second, the 4 most potent RT inhibitors identified were selected as queries for parallel VS performed by combining shape-based, 2D-fingerprint and 3D-pharmacophore VS methods. Overall, a set of molecules characterized by new different scaffolds were identified as novel inhibitors of both HIV-1 RT-associated activities in the low micromolar range.


An analysis of codon utilization patterns in the chloroplast genomes of three species of Coffea.
The chloroplast genome of plants is known for its small size and low mutation and recombination rates, making it a valuable tool in plant phylogeny, molecular evolution, and population genetics studies. Codon usage bias, an important evolutionary feature, provides insights into species evolution, gene function, and the expression of exogenous genes. Coffee, a key crop in the global tropical agricultural economy, trade, and daily life, warrants investigation into its codon usage bias to guide future research, including the selection of efficient heterologous expression systems for coffee genetic transformation. Analysis of the codon utilization patterns in the chloroplast genomes of three Coffea species revealed a high degree of similarity among them. All three species exhibited similar base compositions, with high A/T content and low G/C content and a preference for A/T-ending codons. Among the 30 high-frequency codons identified, 96.67% had A/T endings. Fourteen codons were identified as ideal. Multiple mechanisms, including natural selection, were found to influence the codon usage patterns in the three coffee species, as indicated by ENc-GC3s mapping, PR2 analysis, and neutral analysis. Nicotiana tabacum and Saccharomyces cerevisiae have potential value as the heterologous expression host for three species of coffee genes. This study highlights the remarkable similarity in codon usage patterns among the three coffee genomes, primarily driven by natural selection. Understanding the gene expression characteristics of coffee and elucidating the laws governing its genetic evolution are facilitated by investigating the codon preferences in these species. The findings can enhance the efficacy of exogenous gene expression and serve as a basis for future studies on coffee evolution.


Methyltransferase-inhibition interferes with neuronal differentiation of P19 embryonal carcinoma cells.
We have analyzed the importance of substrate methylation by S-adenosylmethionine-dependent methyltransferases for neuronal differentiation of P19 embryonal carcinoma cells. We show that treatment of cells with methyltransferase inhibitor adenosine dialdehyde (AdOx) interferes with neuronal differentiation. Retinoic acid (RA) and AdOx co-treated cells had a decreased number of neurites and a flattened morphology compared with cells differentiated by RA. Also, the amount of neuronal class III tubulin (Tuj1) decreased from 76% to 9.6% with AdOx-treatment. Gene expression levels of wnt-1, brn-2, neuroD, and mash-1 were also down-regulated by AdOx-treatment. But AdOx-treatment did not up-regulate BMP-4 and GFAP genes. Treatment of RA decreased E-cadherin expression during neuronal differentiation. However, in AdOx/RA co-treated cells, E-cadherin expression was restored to the control level. Also, mRNA expression of N-cadherin decreased with AdOx-treatment. Taken together, these data show that methylation reactions might influence the cell-fate decision and neuronal differentiation of P19 cells.


Amniotic fluid B12 and folate levels associated with neural tube defects.
Amniotic fluid levels of B12 and folate in neural tube defect (NTD) affected pregnancies were compared with the weekly group mean +/-SD changes in amniotic fluid B12 and folate levels of 10 unaffected pregnancies each week between 15 and 20 weeks' gestation age. Comparison was by analysis of variance (ANOVA) and Pearson's correlation to B12 and folate levels and to the NTD samples of corresponding gestation age. Amniotic fluid B12 and folate decreased 67 and 62%, respectively, between 15 and 20 weeks' gestation in the unaffected pregnancies, associated with an increase in amniotic fluid volume. The mean +/-SD B12 and folate of the NTD affected pregnancies (308+/-156 pg/mL and 3.1+/-1.6 ng/mL) were below the mean +/-SD B12 and folate of the total population of unaffected pregnancies (453+/-155 pg/mL and 3.9+/-1.2 ng/mL). The correlation between gestation age and amniotic fluid B12 was -0.9914 (p< or =.0001) and -0.9599 (p< or =.002) for amniotic fluid folate. The B12 levels of the affected pregnancies were below the range of unaffected pregnancies in four of the nine affected pregnancies, and folate levels in two of the nine affected pregnancies.


The relationship between quadriceps muscle weakness and worsening of knee pain in the MOST cohort: a 5-year longitudinal study.
To determine whether quadriceps weakness is associated with elevated risk of worsening knee pain over 5 years. The Multicenter Osteoarthritis Study (MOST) is a longitudinal study of 50-79-year-old adults with knee osteoarthritis (OA) or known risk factors for knee OA. The predictor variable was baseline isokinetic quadriceps strength. Covariates included baseline body mass index (BMI), physical activity level, and history of knee surgery. The outcome was worsening pain reported on the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index pain subscale or knee replacement surgery between baseline and 5-year follow-up. Analyses were knee-based and used generalized estimating equations, stratified by sex to assess whether the lowest compared with the highest tertile of baseline quadriceps strength was associated with an increased risk of worsening knee pain at 5-year follow-up, controlling for age, BMI, history of knee surgery, and physical activity level as well as correlation between knees within participants. Analyses of worsening knee pain included 4,648 knees from 2,404 participants (61% female). Men with lower quadriceps strength did not have a higher risk of worsening knee pain (RR {95% CI} = 1.01 {0.78-1.32}, P = 0.9183). However, women in the lowest compared with the highest strength tertile had a 28% increased risk of worsening knee pain (RR {95% CI} = 1.28 {1.08-1.52}, P = 0.0052). Quadriceps weakness was associated with an increased risk of worsening of knee pain over 5 years in women, but not in men.


Transabdominal repair of cystocele, a 20 year experience, compared with the traditional vaginal approach.
In patients with pelvic floor relaxation and concomitant pelvic pathology indicating the abdominal approach the so-called "combined" operation is not a satisfactory technique. During the course of the total abdominal hysterectomy the cystocele can well be repaired by mobilizing the bladder and excising the relaxed vaginal mucosa. The technique is described and its efficiency in 76 cases is compared to 109 cases repaired by the traditional vaginal approach. Over a 20 year period, 92% of the former as compared to 78% of the latter showed a satisfactory result. Both series revealed that time plus anatomic stress are the major factors in those patients in whom the pelvic floor relaxation recurred.


Olfactory outcomes after endonasal skull base surgery: a systematic review.
For the last two decades, endonasal approach has been regularly applied to treat skull base lesions. However, postoperative olfactory dysfunction remains an unsolved problem. This systematic review aimed to identify factors that might affect postoperative olfactory prognosis of patients undergoing endonasal surgery for resection of sellar/parasellar lesions. The literature search was conducted comprehensively to exhaust studies which focused on patients' olfaction with objective olfactory assessments after endonasal skull base surgery. We sought to characterize the potential factors that might affect postoperative olfactory outcomes. Nineteen articles met inclusion criteria. We found that (1) endoscopic surgery was beneficial to patients' olfactory prognosis than microscopic surgery (incidence of postoperative decreased olfactory function: 18.48% (39/211) for the endoscopic group and 36.88% (52/141) for the microscopic group, P < 0.01); meta-analysis for single rate, 20% (95% CI 9-30%) for the endoscopic group and 35% (95% CI 0-72%) for the microscopic group); (2) harvesting septal flaps was an unfavorable factor for olfactory recovery and the rescue flap technique should be preferred compared with the HB flap; (3) no evidence showed that resection of the middle turbinate was detrimental to recovery of olfaction. Patients undergoing endoscopic endonasal surgery may have better olfactory outcomes than those undergoing microscopic endonasal surgery for resection of sellar/parasellar lesions. Special attention should be paid when using septal flaps is planned and the rescue flap technique should be the preferred choice. After resecting the middle turbinate, patients' olfaction still has a great chance of returning to the baseline. More homogeneous and high-quality studies are needed for further assessment.


The Rearing of Maternal-Fetal Surgery: The Maturation of a Field from Conception to Adulthood.
Maternal-fetal surgery is fraught with inherent controversy from within the medical community and general public. Despite these challenges, the field of maternal-fetal surgery evolved into an international enterprise. Carefully nurtured by pioneers with foresight and resilience, the field navigated ethical dilemmas with rigorous scientific methodology, collaboration, transparency, and accordance. These central pillars are consistent throughout the brief but momentous history of maternal-fetal surgery, serving as the catalyst for its success. The maturation of fetal intervention is an exemplar of technological innovation propelling clinical innovation, as well as a celebration of mastering the delicate balance between caution and optimism.


Resting energy expenditure in patients with isolated head injuries and spontaneous intracranial haemorrhages.
Indirect calorimetry was performed during the first seven days in 39 neurosurgical patients with isolated head injuries (N = 20) and with spontaneous intracranial haemorrhage (N = 19). All patients were artificially ventilated and received total parenteral nutrition during the whole study period. In the trauma group resting energy expenditure (REE) varied from 473-2172 kcal/m(2)/day and in patients with spontaneous haematomas from 552-1591 kcal/m/day. These were 56-265% (trauma) and 61-192% (spontaneous haemorrhages) of predicted basal metabolic rates (BMR). Patients with head injuries showed higher REE values than patients with spontaneous haemorrhage, which was significant (p < 0.001) for the differences between the two study groups and for coma grade II patients. Deeper coma resulted in lower energy expenditure in patients with head injuries but the decrease was significant only from coma grade I to II. The authors conclude that REE rarely exceeds 30% of predicted BMR in patients with spontaneous haemorrhage and 50% in trauma patients. However, the effect of coma on REE should be taken into account when devising nutritional support in this group of patients.


Monomer-oligomer equilibrium of bacteriorhodopsin in reconstituted proteoliposomes. A freeze-fracture electron microscope study.
An improved freeze-fracture electron microscope procedure has been developed and applied to the study of the association of bacteriorhodopsin in large proteoliposomes reconstituted by reverse-phase evaporation with egg lecithin. Due to the improved accuracy and resolution of this procedure, intramembrane particles, the diameter of which (4.5 nm) closely matched that of bacteriorhodopsin monomer, could be observed at high lipid to protein ratios (greater than or equal to 40 w/w). At lower lipid to protein ratios, larger particles (diameter 7.5 nm) progressively appeared, resulting in bimodal particle size distributions up to a lipid to protein ratio of 1, where the large particles were the sole species present. These large particles were interpreted as corresponding to bacteriorhodopsin oligomers. Because of the large size and homogeneity of proteoliposomes, accurate particle density measurements could be performed. These confirmed the occurrence of a lipid to protein ratio-dependent bacteriorhodopsin monomer-oligomer equilibrium and further allowed us to identify the oligomer as a trimer or a tetramer. In complementary experiments, it was found that the bacteriorhodopsin monomer and oligomer had identical visible CD spectra and light-induced proton pumping rates. However, a large increase of the proton passive leak rate of proteoliposomes was found to be associated with oligomer formation. The appearance of these oligomers may be important as the first step in the formation of two-dimensional crystals of bacteriorhodopsin.


The effect of SARS-CoV-2 mRNA vaccination on AMH concentrations in infertile women.
Does SARS-CoV-2 mRNA vaccination affect the ovarian reserve of infertile women undergoing IVF? This was a prospective observational study at a single university-affiliated IVF unit that included infertile women aged 18-44 years who were undergoing IVF/intracytoplasmic sperm injection between November 2020 and September 2021, had received two doses of SARS-CoV-2 mRNA vaccination and had undergone measurement of baseline anti-Müllerian hormone (AMH) concentration within the 12 months preceding their recruitment. AMH concentrations before and after vaccination were evaluated and compared. Overall, 31 women were included in the study. The median AMH concentrations before and after COVID-19 vaccine were comparable (1.7 versus 1.6 g/ml, respectively, P = 0.96). No correlation was found between the participant's anti-COVID-19 antibody titre and the change in AMH concentration. SARS-CoV-2 mRNA vaccination does not adversely affect ovarian reserve, as shown by comparing serum AMH concentrations before and after vaccination. These findings may serve as a counselling tool for clinicians to reassure women undergoing fertility treatment that SARS-CoV-2 mRNA vaccination is safe.


Genetic associations of FCRL3 polymorphisms with the susceptibility of Graves ophthalmopathy in a Chinese population.
Graves ophthalmopathy (GO) is a form of autoimmune thyroid disease commonly found in approximately 25-50% patients with Graves' disease. Both the thyroid-specific genes and immune-modulating genes are involved in susceptibility to GO. However, even though FCRL3 polymorphisms were also autoimmune-associated genes, no study has been performed regarding the association of FCRL3 with GO. Therefore, the objective of the current study was to conduct a basic case-control study in a Chinese population. Seven SNPs were selected in this case-control study and 577 GD patients and 608 controls were recruited. Odds ratio and 95% confidence interval were used to assess the association between susceptibility of GO and FCRL3 polymorphisms with Stata software (Version 11.0, Stata Corp LP, USA). The case-control analysis showed that three polymorphisms, FCRL3_3C, FCRL3_5C, FCRL3_6A, were significantly associated with raised risk of GO in a Chinese Han population in the allelic model [OR = 1.28, 95% CI: 1.09-1.51, P = 0.003; OR = 1.26, 95% CI: 1.07-1.48, P = 0.005; OR = 1.25, 95% CI: 1.06-1.47, P = 0.007]. This case-control analysis confirmed that the FCRL3_3, FCRL3_5 and FCRL3_6 polymorphisms were associated with significantly increased risk of GO in a Chinese population.


Integrative analyses of miRNA and proteomics identify potential biological pathways associated with onset of pulmonary fibrosis in the bleomycin rat model.
To determine miRNAs and their predicted target proteins regulatory networks which are potentially involved in onset of pulmonary fibrosis in the bleomycin rat model, we conducted integrative miRNA microarray and iTRAQ-coupled LC-MS/MS proteomic analyses, and evaluated the significance of altered biological functions and pathways. We observed that alterations of miRNAs and proteins are associated with the early phase of bleomycin-induced pulmonary fibrosis, and identified potential target pairs by using ingenuity pathway analysis. Using the data set of these alterations, it was demonstrated that those miRNAs, in association with their predicted target proteins, are potentially involved in canonical pathways reflective of initial epithelial injury and fibrogenic processes, and biofunctions related to induction of cellular development, movement, growth, and proliferation. Prediction of activated functions suggested that lung cells acquire proliferative, migratory, and invasive capabilities, and resistance to cell death especially in the very early phase of bleomycin-induced pulmonary fibrosis. The present study will provide new insights for understanding the molecular pathogenesis of idiopathic pulmonary fibrosis.


A dominant lethal study in male rats after repeated exposures to vinyl chloride or vinylidene chloride.
Male CD rats were exposed 6 hr/day for 5 days/wk to 0, 50, 250, or 1,000 ppm of vinyl chloride or 55 ppm of vinylidene chloride. Starting on week 11 of exposure, these males were mated with untreated females. There was no evidence of either preimplantation loss or postimplanation loss in pregnant females that resulted from these matings. Consequently, it was concluded that these exposures did not produce germinal mutation, as manifested by a dominant lethal effect, in male rats.


Comprehensive characterization of the effects of ellagic acid and urolithins on colorectal cancer and key-associated molecular hallmarks: MicroRNA cell specific induction of CDKN1A (p21) as a common mechanism involved.
Ellagitannins, ellagic acid, and the colonic metabolites urolithins (Uros) exhibit anticancer effects against colon cells, but a comprehensive molecular analysis has not been done. Herein, we used a panel of cell lines to first time evaluate the antiproliferative properties and accompanying molecular responses of two ellagitannin metabolites mixtures mimicking the situation in vivo and of each individual metabolite. We examined cell growth, cell cycle, apoptosis, and the expression of related genes and microRNAs (miRs) in a panel of nonmalignant and malignant colon cell lines. Regardless of the composition, the mixed metabolites similarly inhibited proliferation, induced cycle arrest, and apoptosis. All the metabolites contributed to these effects, but Uro-A, isourolithin A, Uro-C, and Uro-D were more potent than Uro-B and ellagic acid. Despite molecular differences between the cell lines, we discerned relevant changes in key cancer markers and corroborated the induction of CDKN1A (cyclin-dependent kinase inhibitor 1A gene (p21, Cip1); encoding p21) as a common step underlying the anticancer properties of Uros. Interestingly, cell-unique downregulation of miR-224 or upregulation of miR-215 was found associated with CDKN1A induction. Physiologically relevant mixtures of Uros exert anticancer effects against colon cancer cells via a common CDKN1A upregulatory mechanism. Other associated molecular responses are however heterogeneous and mostly cell-specific.


Purse-string suture combined with subcision and dermal graft for the treatment of wide depressed scars and boxcars.
Dermal layer injuries can result in depressed or indented scars even when there is no subcutaneous injury. These scars can result from acne, chickenpox, trauma, or skin infection. Several procedures, including primary closure, subcision, microneedling, and dermal grafting, have been reported to be used to treat depressed scars, boxcars, or acne cosmetics. These procedures have not, however, been shown to be very effective when applied to the treatment of deep depressed scars, boxcars, or acne cosmetics. In this retrospective study, we assessed scar improvement in patients with deep depressed facial scars and boxcars treated with our novel combination of techniques. This study included all patients treated for deep depressed scars and boxcars at our clinic from 2018 to 2021. To be included, patients had to present in our clinic for the treatment of deep depressed scars or boxcars, have no prominent subcutaneous layer injury, and have full set of clear pre-and post-procedure photographs. All patients initially received technique combination including scar subcision, inner purse-string suturing, and dermal grafting for the first stage surgery treatment. In cases of residual uneven superficial scars, laser dermabrasion resurfacing was used as second-staged treatment. Preoperative and six-month postoperative scar appearance photographs were assessed for improvement by our three nonmedical staff members and divided into four improvement groups, as minimal, moderate, good, and excellent. This study included a total of 24 patients (20 females and four males) with facial scarring. Two patients (8.3%) had moderate, 13 (54.2%) good and nine (37.5%) excellent improvement post-treatment. There were no instances of minimal improvement. Four patients received second stage laser dermabrasion resurfacing for residual uneven superficial scars. We concluded deep depressed scars and boxcars can be easily, safely, and effectively treated using our novel combined scar subcision, inner purse-string suturing, and dermal grafting treatment with possible second-staged laser dermabrasion, and without major complications.


Bacterial chromatin: converging views at different scales.
Bacterial genomes are functionally organized and compactly folded into a structure referred to as bacterial chromatin or the nucleoid. An important role in genome folding is attributed to Nucleoid-Associated Proteins, also referred to as bacterial chromatin proteins. Although a lot of molecular insight in the mechanisms of operation of these proteins has been generated in the test tube, knowledge on genome organization in the cellular context is still lagging behind severely. Here, we discuss important advances in the understanding of three-dimensional genome organization due to the application of Chromosome Conformation Capture and super-resolution microscopy techniques. We focus on bacterial chromatin proteins whose proposed role in genome organization is supported by these approaches. Moreover, we discuss recent insights into the interrelationship between genome organization and genome activity/stability in bacteria.


Two-Step Hydrothermal Preparation of Carbon Dots for Calcium Ion Detection.
It is well known that the calcium ion is essential for maintaining life activities in living organisms, and it is of great significance to detect the intracellular calcium concentration. For the detection of calcium ions, we developed a new type of fluorescent carbon dots (CDs), whose surface was modified by ethylenebis(oxyethylenenitrilo)tetraacetic acid (EGTA) through a secondary hydrothermal method. This is a simple and convenient chemical preparation method because all reactions are carried out in the same autoclave, and the final product is directly the EGTA-modified CDs. The CDs exhibit bright blue fluorescence, and as the calcium concentration increases, the fluorescence intensity drops sharply. The fluorescence quenching correlates with the concentration of calcium ions and has a good linearity in the range of 15-300 μM with a detection limit of 0.38 μM. The experimental results confirmed that the detection of calcium ions by CDs is a static fluorescence quenching process. Also, cytotoxicity test and cellular imaging experiments have shown that the CDs are nontoxic and biocompatible.


Outpatient intravenous antibiotic therapy for endocarditis.
The clinical spectrum of endocarditis continues to evolve, as does its diagnosis and management. Outpatient parenteral antimicrobial therapy has been demonstrated to be safe and effective for medically stable patients with viridans streptococcal endocarditis. Other carefully selected and monitored patients with infective endocarditis may also be considered for completion of therapy outside the hospital setting.


Lower urinary potassium excretion was associated with higher risk of cerebro-cardiovascular- and renal events in patients with hypertension under treatment with anti-hypertensive drugs.
Hypertension is one of the risk factors for cerebro-cardiovascular and renal (CCR) diseases. High blood pressure is affected by the amount of salt (NaCl) and potassium (K) intake. There are many studies reporting the relationship between urinary sodium or potassium excretion and CCR events or all-cause mortality in general populations. Thus, it is necessary to investigate the relationship between urinary NaCl or K excretion and CCR events or all-cause mortality in hypertensive patients under control with anti-hypertensive drugs. A prospective, multi-center cohort study was performed in 3210 hypertensives under treatment with anti-hypertensive drugs for 5 years. The primary outcome was the CCR events, and the secondary outcome was all-cause mortality. A time-dependent Cox proportional hazards regression analysis was performed to assess the association between outcomes and urinary NaCl and K excretion, blood pressure, or heart rate. During the follow-up period, 61 CCR events and 110 all-cause deaths occurred. There was no association between urinary NaCl excretion and CCR events or all-cause mortality. Lower urinary K excretion and higher Na/K ratio were associated with higher risk of CCR events or all-cause mortality. The CCR events were not associated with systolic, diastolic blood pressure, or heart rate. Lower urinary K excretion was associated with higher risk of CCR events or all-cause mortality in hypertensive patients under treatment with anti-hypertensive drugs.


Concentrations and patterns of hydroxylated polybrominated diphenyl ethers and polychlorinated biphenyls in arctic foxes (Vulpes lagopus) from Svalbard.
Concentrations and patterns of hydroxylated (OH) polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) were investigated in liver from arctic foxes (Vulpes lagopus) sampled from Svalbard 1997-2011 (n = 100). The most important OH-PBDE in the arctic foxes was 6-OH-BDE47 detected in 24% of the samples. Relationships between 6-OH-BDE47, δ(13)C and BDE47 suggest that 6-OH-BDE47 residues in arctic foxes are related to marine dietary input, while the relative importance of the metabolic/natural origin of this compound remains unclear. 4-OH-CB187 and 4-OH-CB146 were the main OH-PCBs among the analyzed compounds. The OH-PCB pattern in the present arctic foxes indicates that arctic foxes have a capacity to biotransform a wide range of PCBs of different structures. Formation and retention of OH-PCBs was tightly related to PCB exposure. Furthermore, ΣOH-PCB concentrations were four times higher in the leanest compared to the fattest foxes. Concentrations of 4-OH-CB187 and 4-OH-CB146 among the highest contaminated arctic foxes were similar to the previously reported concentrations for polar bears. Given the high endocrine disruptive potential of OH-PCBs, we suggest that endocrine system may be affected by the relatively high OH-PCB residues in the Svalbard arctic fox population.


Effectiveness of home-based exercise delivered by digital health in older adults: a systematic review and meta-analysis.
regular physical exercise is essential to maintain or improve functional capacity in older adults. Multimorbidity, functional limitation, social barriers and currently, coronavirus disease of 2019, among others, have increased the need for home-based exercise (HBE) programmes and digital health interventions (DHI). Our objective was to evaluate the effectiveness of HBE programs delivered by DHI on physical function, health-related quality of life (HRQoL) improvement and falls reduction in older adults. systematic review and meta-analysis. community-dwelling older adults over 65 years. exercises at home through DHI. physical function, HRQoL and falls. twenty-six studies have met the inclusion criteria, including 5,133 participants (range age 69.5 ± 4.0-83.0 ± 6.7). The HBE programmes delivered with DHI improve muscular strength (five times sit-to-stand test, -0.56 s, 95% confidence interval, CI -1.00 to -0.11; P = 0.01), functional capacity (Barthel index, 5.01 points, 95% CI 0.24-9.79; P = 0.04) and HRQoL (SMD 0.18; 95% CI 0.05-0.30; P = 0.004); and reduce events of falls (odds ratio, OR 0.77, 95% CI 0.64-0.93; P = 0.008). In addition, in the subgroup analysis, older adults with diseases improve mobility (SMD -0.23; 95% CI -0.45 to -0.01; P = 0.04), and balance (SMD 0.28; 95% CI 0.09-0.48; P = 0.004). the HBE programmes carried out by DHI improve physical function in terms of lower extremity strength and functional capacity. It also significantly reduces the number of falls and improves the HRQoL. In addition, in analysis of only older adults with diseases, it also improves the balance and mobility.


Socioeconomic differences persist in use of permanent vs long-acting reversible contraception: An analysis of the National Survey of Family Growth, 2006 to 2010 vs 2015 to 2017.
Permanent contraception has historically been more prevalent among non-White women with lower education and income. Given increasing popularity of long-acting reversible contraception (LARC), we examine changing sociodemographic patterns of permanent contraception and LARC. We performed a descriptive analysis of the National Survey of Family Growth (NSFG) from 2006 to 2017, with multivariable analyses of the 2006 to 2010 and 2015 to 2017 cohorts. Using multinomial logistic regression, we investigate predictors of contraceptive category (permanent contraception vs LARC, lower-efficacy contraception vs LARC) in reproductive-aged women. Total 8161 respondents were included in 2 distinct but analogous regression analyses: (1) the most recent survey cohort, 2015 to 2017 and (2) the cohort a decade prior, 2006 to 2010. Over this period, the prevalence of LARC increased nearly 3-fold (6.2%-16.7%), while permanent contraception use trended downwards (22%-18.6%). Yet, in adjusted models, we observed little change in the sociodemographic predictors of permanent contraception: from the early to recent cohort, use of permanent contraception (vs LARC) remained less likely among college graduates (multinomial odds ratio (OR) 0.45 [95% confidence interval 0.21, 0.97]) and Hispanic women (OR 0.41 [0.21, 0.82]). In addition, high income (>$74,999) and metropolitan residence came to predict less use (OR 0.33 [0.13, 0.84] and 0.47 [0.23, 0.97]). Multiparity, advanced age (over ≥35), and marital status remained strong predictors of permanent contraception. Although use of LARC nearly equals that of permanent contraception in the most recent NSFG survey, socioeconomic differences persist. Continued effort is needed to detect and address structural barriers to accessing the most effective forms of contraception for women. Comparing 2006-2010 to 2015-2017, reliance on female permanent contraception decreased while LARC use increased, making prevalence more similar. However, significant socioeconomic differences persist in who chooses permanent contraception, with urban, educated, higher income women more likely to use LARC. Ongoing efforts are needed to understand and reduce economic barriers to LARC.


Investigation of the Antioxidant Capacity, Insecticidal Ability and Oxidation Stability of Chenopodium formosanum Seed Extract.
To maximize the extraction of antioxidants from Chenopodium formosanum seeds, the process factors, such as the ethanol concentration (0⁻100%), extraction time (30⁻180 min) and temperature (30⁻70 °C), for the extraction of the bioactive contents as well as the antioxidant capacity are evaluated using response surface methodology (RSM). The experimental results fit well with quadratic models. The extract was identified by GC/MS, and it was found that some active compounds had antioxidant, repellency and insecticidal activities. Various concentrations of the extract were prepared for the evaluation of the insecticidal activity against Tribolium castaneum, and the toxicity test results indicated that the extract was toxic to Tribolium castaneum, with an LC50 value of 354.61 ppm. The oxidative stability of the olive oil determined according to the radical scavenging activity and p-anisidine test demonstrates that the extract obtained from the Chenopodium formosanum seeds can retard lipid oxidation.


Rasagiline monotherapy in early Parkinson's disease: A phase 3, randomized study in Japan.
Rasagiline is a monoamine oxidase type-B inhibitor in development in Japan for Parkinson's disease (PD). The objective of this Phase 3, randomized, double-blind study was to evaluate the efficacy and safety of rasagiline in Japanese patients with early PD (NCT02337725). Patients were 30-79 years old with a diagnosis of PD within 5 years. Following a two-week placebo run-in period, patients were randomized 1:1 to receive rasagiline (1 mg/day) or placebo for up to 26 weeks. The primary endpoint was change from baseline in the MDS-UPDRS Part II + III total score (TS). Secondary endpoints included the MDS-UPDRS Parts II + III, III, II, and I TS and safety. In total, 118 patients were randomized to rasagiline and 126 to placebo. Patient characteristics at baseline were similar in both groups. The change from baseline in the MDS-UPDRS Part II + III TS was significantly greater in the rasagiline vs. placebo group (rasagiline-placebo: -6.39, 95% CI: -8.530, -4.250; P < 0.0001). The mean changes from baseline in the MDS-UPDRS Part II + III, Part III and Part II TS were lower at treatment visits between weeks 6 and 26 in the rasagiline vs. placebo groups. The overall incidence of treatment-emergent adverse events (TEAEs) was 62.4% and 52.4% in the rasagiline and placebo groups, respectively; most frequent TEAE was nasopharyngitis (15.4% and 15.1%). Treatment with oral rasagiline 1 mg/day was effective and well-tolerated in Japanese patients with early PD, with a significantly greater improvement in the MDS-UPDRS Part II + III TS vs. placebo, and a similar safety profile.


Comparison of Single Port Access Versus Multiple Port Access Systems in Elective Laparoscopy: 98 Dogs (2005-2014).
To report and compare the duration of surgery, the frequency of complications, and the frequency of open conversion for elective surgeries performed with 2 laparoscopic techniques: a single incision port access system (SPAS) and a multiple port access system (MPAS) using a Veress needle. Retrospective case series. Ninety-eight consecutive, client owned dogs. Medical records of dogs undergoing an elective laparoscopic procedure were reviewed. Dogs were classified as SPAS or MPAS according to the initial surgical approach. Duration of surgery, intraoperative complications, reason for open conversion, and postoperative complications were recorded and compared. The duration of surgery for SPAS gastropexy (P = .0039), ovariectomy (P = .0052), and gastropexy/ovariectomy combined (P = .0002) were significantly reduced compared to corresponding MPAS procedures. Nine splenic punctures occurred during MPAS. The frequency of intraoperative complications was significantly less for SPAS (0/44) than MPAS (12/54, P = .004). Elective conversion was performed because of gastric malpositioning in 1 dog and emergent conversion was required because of bleeding from the ovarian pedicle in 2 dogs (0/44 SPAS, 3/54 MPAS, P = .250). There were 14/76 dogs with followup to suture removal with postoperative complications, all incisional (7/31 SPAS, 7/45 MPAS, P = 1.0). The use of SPAS for laparoscopy reduced surgical time and intraoperative complications in elective procedures.