Evaluation of physical health in an in-patient psychiatric rehabilitation setting.
The mortality gap between patients with and without serious mental illness (SMI) is around 15-20 years. Here, we aim to identify some of the factors contributing to that gap via poor physical health and sub-optimal medical management. We report the results of a detailed cross-sectional study of physical health parameters in an in-patient rehabilitation population in Scotland, including a consideration of concordance with guidelines and comparisons to healthy populations. Data was collected from 57 of all 62 in-patients. 42% were obese (compared to 28% of the population), 84% were smokers (vs 16%), 16% were hypertensive, 22% had raised HbA1c, 50% had raised cholesterol, 47% had QRISK >10%. 68% agreed to a full physical health review, 65% agreed to flu vaccination. Completed screening uptake compared to the Scottish population was low: Cervical (30% vs 69%), Bowel (8% vs 64%), Breast (23% vs 72%), Abdominal Aortic Aneurysm (0% vs 78%). Patients generally had up to date recorded weight (100%), blood pressure (98.2%), heart rate (98.2%) and lipids (89.4%), but not ECG's (61.4%) or Diabetes screening (59.6%). Following review, 17 referrals were made to medics/surgeons, 29 to broader specialties, 24 medications were started, 9 stopped and 27 changed: most commonly statins (12 patients), vitamin D (8 patients) and hypoglycemics (5 patients). The findings highlight cardiovascular risk factors and cancer screening as specific areas to target for improving poor physical health in populations with SMI. Patients are often willing to engage but specific ways to lower the barriers to screening and treatment are required.


Comparison of three fixation techniques for arcuate fractures.
Proximal fibula avulsion fractures, or "arcuate fractures", are an often discussed but poorly defined injury pattern which represent a destabilizing injury to the posterolateral corner of the knee. Historical and recent literature discussing reconstruction and repair techniques exist, but there has been little biomechanical evaluation of repair techniques. The purpose of this study was to evaluate the strength of three type of fixation techniques for arcuate fractures: bone tunnels, a screw and washer, and a novel suture anchor technique. A laboratory model of the arcuate fracture pattern was developed. This was used to create an arcuate fracture in 24 cadaveric specimens. Knees were randomized into fixation with either suture tunnel (ST), screw and washer (SW), or suture anchor (SA) repair. A previously published model for inducing varus stress was applied and a MTS testing system was used to assess fixation ultimate and yield strength. Fibular fracture occurred during the fixation of one specimen from the ST group and one from the SA group. Analysis of the remaining 22 specimens revealed a mean ultimate strength of 2422.48 N for the ST group, 2271.78 for SW, and 3041.66 for SA (p = 0.390). Yield strengths were 2065.28 for ST, 1882.43 for SW, and 2871.92 for SA (p = 0.224). Analyses of stiffness and total energy applied were not statistically different (p = 0.111 and 0.601, respectively). Biomechanical analysis of three types of arcuate fragment fixation revealed robust fixation among all methods, supporting surgeon preference for fixation. Fixation may depend on the size of bony fragment and whether or not the injury is a bony or soft tissue injury.


Rebleeding of aneurysmal subarachnoid hemorrhage in computed tomography angiography: risk factor, rebleeding pattern, and outcome analysis.
For patients with subarachnoid hemorrhage (SAH), computed tomography angiography (CTA) has been the first imaging modality for aneurysm detection. We evaluate the rate, time distribution, risk factors, and clinical outcome of aneurysmal rebleeding by CTA findings. Consecutive patients with SAH presenting to our hospital, a tertiary care hospital, were retrospectively included. We reviewed images for all patients receiving an initial noncontrast computed tomography scan and further CTA for nontraumatic SAH surveillance with focus on rebleeding evidence. A total of 12 patients with early aneurysmal rebleeding (12/110 patients [10.9%]) within 6 hours after emergency room arrival were found with dismal outcome (50% mortality) and 3 rebleeding patterns: pattern 1 of rapid active bleeding with contrast extravasation, pattern 2 of slow active bleeding with contrast leakage in the delayed venous phase, and pattern 3 of hematoma enlargement. The risk factor and poor prognostic sign include larger aneurysm diameter (≧7 mm) and contrast extravasation during CTA. Rebleeding rate of aneurysmal SAH in the hyperacute stage at less than 6 hours is 10.9% with poor prognosis in this study, especially in patients with active bleeding demonstrated in CTA.


Relationship between injection duration, transporter occupancy and reinforcing strength of cocaine.
Among drugs that can function as positive reinforcers, slower occupancy of central nervous system sites of action has been associated with diminished reinforcing strength. The present study examined the relative reinforcing strength of cocaine, and the rate of in vivo dopamine transporter binding, as a function of injection duration. Rhesus monkeys (N=5) were allowed to self-administer cocaine under a progressive-ratio schedule with doses injected over different times (10-600 s). An ex vivo dopamine transporter binding assay was used to examine kinetics of in vivo transporter occupancy by cocaine injected over the same times in rats. Cocaine was a weaker reinforcer, and dopamine transporter binding rate decreased, with slower injections. Maximum transporter binding was the same across injection durations. These results support the hypothesis that slower onset of action is associated with a slower transporter occupancy and diminished reinforcing strength. Relative strength as a reinforcer may not be determined by maximum occupancy, at least not exclusively.


Posterior wall fractures associated with both-column acetabular fractures can be skilfully ignored.
Posterior wall fractures may be associated with both-column acetabular fractures. Considering the differences in the pattern of these fractures in contrast to isolated posterior wall fractures, it is currently unclear whether they can be ignored or need to be addressed surgically. Stable posterior wall fractures can be skilfully ignored in patients with both-column acetabular fractures operated by an ilioinguinal approach. We retrospectively reviewed 49 consecutive patients who were treated for both-column acetabular fractures between the years 2009 and 2018. Considering the association of posterior wall fractures, we divided the cohort into two groups: Group 1 (n=29): absence of posterior wall fractures; and Group 2 (n=20): presence of posterior wall fractures, subsequently treated while skilfully ignoring stable posterior wall fracture according to our criteria. Intergroup comparison of radiologic and clinical outcomes and multiple linear regression for predictors of clinical outcomes were analysed. No significant intergroup difference in quality of reduction, post-traumatic osteoarthritis grade, or clinical outcome was noted. Poor post-traumatic osteoarthritis grade and poor quality of reduction of both acetabular columns were significant predictors of clinical outcomes in patients with both-column acetabular fractures. Whether posterior wall fracture was associated and skilfully ignored was unrelated to clinical outcomes. Posterior wall fractures associated with both-column acetabular fractures can be successfully ignored if the posterior wall fragment is adequately attached to the acetabulum through the labrocapsular complex of the hip joint, and the hip-joint-congruency in the presence of<2-mm step-off and 3-mm gap. III, prognostic.


Spinal surgery in the treatment of metastatic back pain: three case reports.
Back pain resulting from spinal instability in metastatic bone disease can be difficult to alleviate by pharmacological methods and surgical intervention is frequently required. This paper discusses the treatment options with three illustrative case reports.


Coronary spasm producing coronary thrombosis in a patient with acute myocardial infarction.
A 62-year-old man had an acute myocardial infarction with successful thrombolysis. Coronary spasm was documented in the following angiographic study. This case demonstrated that coronary spasm is implicated in the pathogenesis of coronary thrombosis and subsequent myocardial infarction.


Stereotactic Body Radiation Therapy for Lung Metastases From Sarcoma in Oligometastatic Patients: A Phase 2 Study.
The lung is the most frequent site of metastasis in patients with sarcoma. Pulmonary metastasectomy is the most common treatment performed. Stereotactic body radiation therapy (SBRT) has proven to be a potential alternative to resection. This prospective phase 2 study aimed to assess the role of SBRT for patients with lung metastases. Adult patients with up to 4 lung metastases (LMs) ≤5 cm in diameter and unsuitable for surgery were included. Dose prescription was based on site and size: 30 Gy/1 fraction for peripheral lesions ≤10 mm, 60 Gy/3 fractions for peripheral lesions 11 to 20 mm, 48 Gy/4 fractions for peripheral lesions >20 mm, and 60 Gy/8 fractions for central lesions. The primary endpoint was the proportion of treated lesions free from progression at 12 months. Secondary endpoints were disease-free survival (DFS), overall survival (OS), and toxicity. Between March 2015 and December 2020, 44 patients with a total of 71 LMs were enrolled. Twelve-month local control was 98.5% ± 1.4%, reaching the primary aim; the median DFS time was 12 months (95% CI, 8-16 months), and the 1-, 2-, 3-, 4-, and 5-year PFS rates were 50% ± 7.5%, 19.5% ± 6.6%, 11.7% ± 5.8%, 11.7% ± 5.8%, and 11.7% ± 5.8%, respectively. The median OS time was 49 months (95% CI, 24-49 months), and the 1-, 2-, 3-, 4-, and 5-year OS rates were 88.6% ± 4.7%, 66.7 ± 7.6%, 56.8% ± 8.4%, 53.0% ± 8.6%, and 48.2% ± 9.1%, respectively. Prognostic factors recorded as significantly affecting survival were age, grade of primary sarcoma, interval time from diagnosis to occurrence of LMs, and number of LMs. No severe pulmonary toxicity (grade 3-4) occurred. The study found a local control of LMs in almost all patients treated, with negligible toxicity. Survival was also highly satisfactory. Well-designed randomized trials comparing surgery with SBRT for patients with metastatic lung sarcoma are needed to confirm these preliminary data.


Risk factors for herpes zoster infection among Filipinos with systemic lupus erythematosus.
To identify clinical risk factors associated with herpes zoster (HZ) infections in systemic lupus erythematosus (SLE). A case-control study of HZ infection was performed in SLE patients seen at the University of Santo Tomas Lupus Clinics from 2009-2014. Cases were matched 1:2 to SLE controls without HZ infection for age, sex, and disease duration. Clinical characteristics, SLE disease activity, and immunosuppressive use were compared. Sixty-five SLE patients (61, 93.8% female) who developed HZ were matched with 130 SLE patients without HZ. Mean age was 36.75 years (±1.35; P = 1.00) for the case group; mean SLE disease duration at first HZ infection was 6.1 years (±3.3; P = .919). Four patients had more than 1 episode of HZ. There was localized HZ in 63/65 (97%), and 2 (3%) disseminated HZ infections. The case group received higher doses of prednisone 64/65 (P = .012), mean prednisone dose 18.62 mg/d (±1.48, P < .001) and more were exposed to cyclophosphamide (Cyc) (19/65; P < .001) compared to the control group's mean prednisone dose of 11.73 mg/d (±1.16); there was Cyc use in 7/130 patients. Cyc in addition to mycophenolate mofetil (MMF) use among lupus nephritis patients conferred the highest risk for HZ infection occurrence. Hydroxychloroquine (HCQ) use reduced the risk for HZ by 87% (adjusted odds ratio 0.13, P = .003). Immunosuppressives and corticosteroid use are risk factors associated with the development of HZ in SLE. The risk for HZ increases among patients given intravenous Cyc and MMF for lupus nephritis. SLE disease activity did not show a direct association with HZ occurrence. HCQ use appeared to have a protective role against HZ infection.


[Viral infection and sudden perceptive deafness (serological examinations) (author's transl)].
Among the numerous and various known etiologies of sudden deafness viral infection is discussed. Therefore sera of 126 patients were examined for viral antibodies to Influenza, Parainfluenza, Mumps, Measles, RS-virus, Rubella, Herpesvirus and Adenovirus. They were compared to sera of healthy patients. Our results suggest no strong association between sudden deafness and viral infection.


Congenital laryngeal atresia associated with partial diaphragmatic obliteration.
Laryngeal atresia is a rare, life-threatening congenital malformation. Prenatal sonographic diagnosis has been described; however, in many cases, the precise diagnosis is established only at autopsy. Our aim was to describe an atypical prenatal presentation of congenital laryngeal atresia in which the final diagnosis was made only at autopsy. Sonographic and postmortem examinations were performed on a fetus with bilateral enlarged echogenic lung fields, an everted diaphragm, and polyhydramnios, which were initially noted on prenatal sonography at 26 weeks' gestation. Unfortunately, the mother was lost to follow up at our inner-city clinic, thus precluding a definitive diagnosis. At birth, tracheostomy was not performed because of the anomalous appearance of the neonate and the suspicion of multiple congenital anomalies. Neonatal death occurred after 18 minutes of life. Autopsy revealed laryngeal atresia with a right hemidiaphragmatic defect and multiple other congenital anomalies. This was a rare case with prenatal sonographic findings in a fetus with congenital laryngeal atresia associated with partial diaphragmatic obliteration.


The Application of Biometric Approaches in Agri-Food Marketing: A Systematic Literature Review.
A challenge in social marketing studies is the cognitive biases in consumers' conscious and self-reported responses. To help address this concern, biometric techniques have been developed to obtain data from consumers' implicit and non-verbal responses. A systematic literature review was conducted to explore biometric applications' role in agri-food marketing to provide an integrated overview of this topic. A total of 55 original research articles and four review articles were identified, classified, and reviewed. It was found that there is a steady growth in the number of studies applying biometric approaches, with eye-tracking being the dominant method used to investigate consumers' perceptions in the last decade. Most of the studies reviewed were conducted in Europe or the USA. Other biometric techniques used included facial expressions, heart rate, body temperature, and skin conductance. A wide range of scenarios concerning consumers' purchase and consumption behaviour for agri-food products have been investigated using biometric-based techniques, indicating their broad applicability. Our findings suggest that biometric techniques are expanding for researchers in agri-food marketing, benefiting both academia and industry.


Molecular cloning and characterization of secretogranin II in the catfish Heteropneustes fossilis: Sex and seasonal brain regional variations and its gonadotropin regulation.
Secretoneurin (SN) is a novel functional peptide derived from secretogranin II, a protein belonging to the class of chromogranins. Catfish Heteropneustes fossilis is an economically important species of the Asian subcontinent and holds an important place in reproductive physiology study. In the present study, the full-length cDNA encoding secretogranin IIb (SgIIb) was cloned from the brain of catfish H. fossilis. Sequence analysis showed that a 33 amino acid SN peptide (SNb) is present in SgIIb proprotein. The full-length sequence of SgIIb is 2912 bp with open-reading frame 1761 bp long. The 5'UTR is 681 bp long upstream and the 3'UTRis 470 bp long downstream. The ORF encodes 586 amino acid residues comprising signal peptide (24 amino acids) and SNb (33 amino acids), EM66 (66 amino acids). Catfish SgIIb showed 88% nucleotide homology and 90% protein identity with Ictalurus punctatus. Tissue expression showed that it is highly expressed in the brain among all tissues studied. In situ hybridization and quantitative real-time PCR showed significant brain regional distribution with highest transcript abundance in the pituitary. In ovary tissue SgIIb transcripts were localized in the granulosa layer. In the brain, hCG administration stimulated expression highly at 16 h. In ovary, hCG treatment under in vivo and in vitro condition decreased SgIIb expression at all doses. Thus, in the present study in situ localization of SgIIb mRNAs in different regions of brain and pituitary, and ovary suggest its putative role in regulating hypothalamic-pituitary-gonadal (HPG) axis and also suggest that the SgIIb expression pattern in the brain and ovary could be related to reproductive activity and may be involved in the neuroendocrine role of SgIIb in the catfish H. fossilis.


Mechanisms of increase in amylase activity in rat submandibular and sublingual glands after administration of pilocarpine.
The increase in parotid rather than pancreatic-type amylase activity in the submandibular and sublingual glands of rats caused by administration of pilocarpine was abolished or diminished when pilocarpine was injected into rats which had been parotidectomized, sympathectomized by superior cervical ganglionectomy or pretreated with reserpine. These results suggest that the increases in amylase activity in the submandibular and sublingual glands by pilocarpine are not due to increase in enzyme synthesis, but to uptake of enzyme released into the blood in large quantities from the parotid gland and that the release from the parotid gland by pilocarpine is primarily mediated by sympathetic nerves.


Isotopic and elemental characterisation of Slovenian apple juice according to geographical origin: Preliminary results.
This study examined the applicability of stable isotope and multi-element data for determining the geographical origin of fresh apple juices. Samples included three apple cultivars (Idared, Golden Delicious and Topaz) harvested in 2011 and 2012 from five different geographical regions of Slovenia. Regional discrimination of the juice samples was most successful when using linear discriminant analysis (LDA) and taking into account the following parameters: δ(2)H and δ(18)O content of juice water; δ(15)N and δ(13)C content of the pulp, (D/H)I and (D/H)II in ethanol and the concentration of S, Cl, Fe, Cu, Zn and Sr. Overall prediction ability was 83.9%. The factors that best distinguished the different types of cultivar were the δ(2)H and δ(18)O content of fruit juice water; the δ(13)C and (D/H)I content of ethanol; and the concentration of S, Mg, K, Cu, and Ti. Prediction ability, taking into account all ten parameters, was 75.8%.


Opening Up About My Struggle With Recurring Depression.
A health care leader shares her story of living with major depression and calls for better treatments.


Photorefractive keratectomy for myopia in the setting of adenoviral subepithelial infiltrates.
To report a patient with persistent subepithelial corneal opacities 18 months after adenoviral keratoconjunctivitis who underwent photorefractive keratectomy for the correction of myopia. Case report, review of medical literature, and slit-lamp photography. The patient underwent photorefractive keratectomy in each eye, 1 week apart, with ablation of central corneal opacities and resultant best-corrected visual acuity of BE, 20/20. Symptomatic subepithelial stromal infiltrates recurred in the peripheral but not the central cornea of each eye 3 months after laser treatment. Photorefractive keratectomy was successful in the correction of myopia and prevented the recurrence of adenoviral subepithelial corneal infiltrates within the laser-treated central cornea.


Complete hepatitis B virus prophylaxis withdrawal in hepatitis B surface antigen-positive liver transplant recipients after longterm minimal immunosuppression.
Tailored approaches have been attempted to prevent hepatitis B virus (HBV) reinfection in antibodies against hepatitis B surface antigen (HBsAg)-positive liver transplantation (LT) recipients in order to minimize the use of hepatitis B immune globulin (HBIG) and nucleoside analogues (NAs). We report the results of complete HBV prophylaxis withdrawal after a follow-up of at least 6 years in LT recipients with undetectable serum HBV DNA and intrahepatic total HBV DNA and covalently closed circular DNA at LT. We included 30 HBsAg positive, hepatitis B e antigen-negative recipients, 6 with hepatitis C virus and 7 with hepatitis D virus coinfection, who had received HBIG plus NA for at least 5 years after LT. Stepwise HBIG and NA withdrawal was performed in two 6-month periods under strict monitoring of HBV virology. All patients underwent a clinical, biochemical, and virological follow-up at 3-6 month intervals. HBV recurrence (HBsAg seroreversion ± detectable HBV DNA) occurred in 6 patients: in 1 patient after HBIG interruption and in 5 after both HBIG and NA cessation. Only 3 patients required reinstitution of HBV prophylaxis because of persistent HBV replication, and all achieved optimal control of HBV infection and did not experience clinical events. The other who recurred showed only short-lasting HBsAg positivity, with undetectable HBV DNA, followed by spontaneous anti-HBs seroconversion. An additional 15 patients mounted an anti-HBs titer, without previous serum HBsAg detectability. At the end of follow-up, 90% of patients were still prophylaxis-free, 93.3% were HBsAg negative, and 100% were HBV DNA negative; 60% had anti-HBs titers >10 IU/L (median, 143; range, 13-1000). This small series shows that complete prophylaxis withdrawal is safe in patients transplanted for HBV-related disease at low risk of recurrence and is often followed by spontaneous anti-HBs seroconversion. Further studies are needed to confirm this finding. Liver Transplantation 22 1205-1213 2016 AASLD.


Laser capture microdissection and colorectal cancer proteomics.
The ability to define protein profiles of normal and diseased cells is important in understanding cell function. Laser capture microdissection permits the isolation of specific cell types for subsequent molecular analysis. In this study we have established conditions for obtaining proteomic information from laser capture microdissected colorectal cancer cells. Laser capture microdissection was performed on toluidine blue-stained frozen sections of colorectal cancer. Proteins were solubilized from microdissected cells and the solubilized proteins were separated by two-dimensional gel electrophoresis: protein spots were characterized by peptide mass mapping using matrix assisted laser desorption ionization-time of flight mass spectrometry. Proteins isolated from laser capture microdissected tissue retained their expected electrophoretic mobility and peptide mass mapping was also unaffected. The ability to study the protein expression profile of specific cell types will allow for the identification of novel disease markers and therapeutic targets and also provide for the enhanced understanding of pathogenetic mechanisms.


[The emergency service physician and acute abdominal pathology. Comparative study on 1500 cases].
1436 cases of recent abdominal pain encountered in the Casualty Department of Biella Hospital over 18 consecutive months are examined. The incidence of the various abdominal pathologies, the diagnostic and therapeutic procedures adopted in the first hours after admission and any differences between original diagnosis by the general practitioner of the First Aid post, diagnosis on admission and diagnosis on release from hospital are examined.


Caesarean section in a pygmy hippopotamus (Choeropsis liberiensis) and the management of the wound.
A laparohysterotomy was performed on a 17-year-old pygmy hippopotamus (Choeropsis liberiensis) to remove a dead over-sized fetus. The operation was successful and the animal recovered, but the surgical wound broke down and healed slowly by second intention.


Hypermethylation and reduced expression of Gtl2, Rian and Mirg at the Dlk1-Dio3 imprinted locus as a marker for poor developmental potential of mouse embryonic stem cells.
Mouse embryonic stem cells (ESCs) have played a crucial role in biomedical research where they can be used to elucidate gene function through the generation of genetically modified mice. A critical requirement for the success of this technology is the ability of ESCs to contribute to viable chimaeras with germ-line transmission of the genetically modified allele. We have identified several ESC clones that cause embryonic death of chimaeras at mid to late gestation stages. These clones had a normal karyotype, were pathogen free and their in vitro differentiation potential was not compromised. Chimaeric embryos developed normally up to E13.5 but showed a significant decrease in embryo survival by E17.5 with frequent haemorrhaging. We investigated the relationship between the ESCs transcriptional and epigenomic state and their ability to contribute to viable chimaeras. RNA sequencing identified four genes (Gtl2, Rian, Mirg and Rtl1as) located in the Dlk1-Dio3 imprinted locus that were expressed at lower levels in the compromised ESC clones and this was confirmed by qRT-PCR. Bisulphite sequencing analysis showed significant hypermethylation at the Dlk1-Dio3 imprinted locus with no consistent differences in methylation patterns at other imprinted loci. Treatment of the compromised ESCs with 5-azacytidine reactivated stable expression of Gtl2 and rescued the lethal phenotype but only gave low level chimaeras.


Volume-activated chloride channels in HeLa cells are blocked by verapamil and dideoxyforskolin.
The possible role of Cl- currents in regulatory volume decrease processes has been explored in HeLa cells using the whole-cell recording mode of the patch-clamp technique. Cells showed very small currents in voltage-clamp experiments performed with Cl(-)-rich, permeant-cation-free (N-methyl-D-glucamine replacement) intracellular and bathing solutions. Exposure of the cells to hypotonic solutions visibly swelled the cells and activated, reversibly, an outward rectifying Cl- current, which decayed at the most depolarised voltages used. Replacement of extracellular Cl- by a series of halide anions, SCN- and gluconate was consistent with an anion selectivity sequence: SCN- > I- > Br- > Cl- > F- > gluconate. The volume-regulated Cl- current was effectively inhibited by 100 microM 5-nitro-2-(3-phenyl-propylamino)-benzoic acid and by 100 microM 4,4'-diisothiocyanotostilbene-2,2-disulphonic acid, substances known to block Cl- channels in a variety of cells. Chloride current activation by hypotonicity was dependent on the presence of ATP in the intracellular solution and this requirement could be replaced by the non-hydrolysable analogue ATP[gamma S] and Mg(2+)-free ATP. The data suggest that the channels responsible for the current described are involved in the regulatory volume decrease in HeLa cells. The characteristics of this Cl- current are similar to those of the current associated with expression of multidrug resistance P-glycoprotein. Furthermore, the currents in HeLa cells were inhibited rapidly and reversibly by verapamil and 1,9-dideoxyforskolin, which are known to inhibit P-glycoprotein function.


Detection of rare variant effects in association studies: extreme values, iterative regression, and a hybrid approach.
We develop statistical methods for detecting rare variants that are associated with quantitative traits. We propose two strategies and their combination for this purpose: the iterative regression strategy and the extreme values strategy. In the iterative regression strategy, we use iterative regression on residuals and a multimarker association test to identify a group of significant variants. In the extreme values strategy, we use individuals with extreme trait values to select candidate genes and then test only these candidate genes. These two strategies are integrated into a hybrid approach through a weighting technology. We apply the proposed methods to analyze the Genetic Analysis Workshop 17 data set. The results show that the hybrid approach is the most powerful approach. Using the hybrid approach, the average power to detect causal genes for Q1 is about 40% and the powers to detect FLT1 and KDR are 100% and 68% for Q1, respectively. The powers to detect VNN3 and BCHE are 34% and 30% for Q2, respectively.


Research protocol - Assessing Post-Stroke Psychology Longitudinal Evaluation (APPLE) study: A prospective cohort study in stroke.
Cognitive and mood problems have been highlighted as priorities in stroke research and guidelines recommend early screening. However, there is limited detail on the preferred approach.We aimed to (1) determine the optimal methods for evaluating psychological problems that pre-date stroke; (2) assess the test accuracy, feasibility and acceptability of brief cognitive and mood tests used at various time-points following stroke; (3) describe temporal changes in cognition and mood following stroke and explore predictors of change. We established a multi-centre, prospective, observational cohort with acute stroke as the inception point - Assessing Post-stroke Psychology Longitudinal Evaluation (APPLE). We approached patients admitted with stroke or transient ischaemic attack (TIA) from 11 different hospital sites across the United Kingdom. Baseline demographics, clinical, functional, cognitive, and mood data were collected. Consenting stroke survivors were followed up with more extensive evaluations of cognition and mood at 1, 6, 12 and 18 months. Continuous recruitment was from February 2017 to February 2019. With 357 consented to full follow-up. Eighteen-month assessments were completed in September 2020 with permissions in-place for longer term in-person or electronic follow-up. A qualitative study has been completed, and a participant sample biobank and individual participant database are both available. The APPLE study will provide guidance on optimal tool selection for cognitive and mood assessment both before and after stroke, as well as information on prognosis and natural history of neuropsychological problems in stroke. The study data, neuroimaging and tissue biobank are all available as a resource for future research.


Impacts of Coping Mechanisms on Nursing Students' Mental Health during COVID-19 Lockdown: A Cross-Sectional Survey.
The COVID-19 pandemic and consequent lockdown have precipitated significant disruption in the educational system. Nursing students are known to have higher levels of stress and anxiety than other non-nursing students, but there is a dearth of evidence regarding the impacts of the COVID-19 lockdown on their mental health and coping mechanisms. The aim of this study was to explore the influence of coping mechanisms as predictors of stress, anxiety, and depression among nursing students during the COVID-19 lockdown. A cross-sectional online survey was conducted from 20 April to 10 May 2020 among 173 nursing students at a private university in Southern California, USA. Self-reported stress, anxiety, and depression were significantly higher during the lockdown compared to the pre-lockdown period (p < 0.001). Almost a quarter of participants reported high stress, while more than half reported moderate-to-severe symptoms of anxiety and depression. High resilience was negatively associated with high stress (Odds Ratio (OR) = 0.46; 95% Confidence Interval (CI) = 0.22-0.98; p = 0.045), moderate-to-severe anxiety (OR = 0.47; 95%CI = 0.25-0.90; p = 0.022), and moderate-to-severe depression (OR = 0.50; 95%CI = 0.26-0.95; p = 0.036). Similarly, high family functioning was negatively associated with high stress (OR = 0.41; 95%CI = 0.20-0.86; p = 0.018), moderate-to-severe anxiety (OR = 0.41; 95%CI = 0.21-0.80; p = 0.009), and moderate-to-severe depression (OR = 0.41; 95%CI = 0.20-0.81; p = 0.011). High spiritual support was negatively associated with moderate-to-severe depression (OR = 0.48; 95%CI = 0.24-0.95; p = 0.035). During the COVID-19 lockdown, nursing students experienced remarkable levels of poor mental health. High levels of resilience and family functioning were associated with 2- to 2.4-fold lower risk of stress, anxiety, and depression, whereas high spiritual support was associated with 2-fold lower risk of depression. As the pandemic evolves, fostering these coping mechanisms may help students to maintain their psychological wellbeing.


Targeting molecular signals in chk1 pathways as a new approach for overcoming drug resistance.
The common clinical problem in the successful treatment of cancer is the resistance of cancer cells to chemotherapeutic drugs. Chemotherapy kills drug-sensitive cells, but leaves behind a higher proportion of drug-resistant cells. The resistance can be due to altered drug accumulation, retention, metabolism and distribution, or to reduced drug-target interaction. More recently, cell cycle progression, DNA mismatch repair (MMR) and cell death have been shown to play an important role in the regulation of cell resistance to anticancer drugs. Chkl regulation pathways, DNA MMR and p73, as well as altered apoptotic cell death involved in the cell resistance toward DNA damaging agents will be reviewed in this article.


Influential literature regarding proximal junctional kyphosis: A bibliometric review.
Retrospective review. This bibliometric review summarizes the publication trends and critical information about the most cited Proximal Junction Kyphosis (PJK) articles. Data: Proximal junctional kyphosis is frequently diagnosed after spinal fusion surgery. However, there continues to be heavy debate regarding the definition, incidence, risk factors, and treatment of this disorder. Nine hundred eleven articles were found when searching The Web of Science database with the keywords "Proximal junctional kyphosis" and "proximal junctional failure." The 200 top-cited articles were reviewed and screened to ensure PJK was discussed. The articles were filtered based on the highest to lowest number of citations, and the top 50 articles were chosen. Inclusion criteria included articles that contained a discussion of PJK and outcomes after surgery. Exclusion criteria included articles without mentioning PJK, or that studied non-human subjects. The 50 most cited articles were sorted by level of evidence and their classification for analysis. The 50 most cited articles in this study were published a total of 6056 times. These articles were cited 71-413 times in the literature, with publications from 1994 to 2018. Most of the top 50 articles (64%) were published in the USA. Specifically, HSS and Washington University are the institutions with the most contributions to the publication of the most cited articles on PJK (n = 16). Lenke was the author that contributed to most publications in the top 50 articles on PJK. This study provides a framework for the most cited articles published on PJK. Most articles on this topic were in the category of clinical outcomes (36%) and were of a level of evidence III (46%). Most of the top-cited articles came from the journal Spine (68%) and were published in the USA (64%). These top-cited papers are essential to understanding this critical trending topic in spine surgery. III.


Ultrastructural identification of type 1 fibres in human skeletal muscle. Immunogold labelling of thin cryosections with a monoclonal antibody against slow myosin.
Existing methods for the ultrastructural identification of fibre types in human skeletal muscle are fallible. This has prompted us to develop a reliable immunoelectron microscopic approach for the identification of human skeletal muscle fibre types. Here we report the unambiguous electron microscopic identification of human type 1 muscle fibres, achieved by combining cryoultramicrotomy with colloidal gold immunocytochemical labelling, using a monoclonal antibody (N0Q7.5.4D) which is specific for the heavy chain of the slow myosin isoform of human skeletal muscle. This method for the identification of muscle fibre types and determination of myosin isoform distributions may have important applications in the ultrastructural study of pathological muscle and in the analysis of myofibrillar assembly during myogenesis.


Early calcitonin hypersecretion and C cell hyperplasia in rats with high incidence of C cell tumors (Wag/Rij).
Wag/Rij rats, a Wistar-derived strain, develop on aging a spontaneous medullary thyroid carcinoma which shows many morphological similarities to the human neoplasm. Using biochemical and histological methods, we studied calcitonin secretion and C cell distribution in young and adult Wag/Rij rats, to characterize possible modifications in calcitonin synthesis and secretion as compared to the original Wistar strain. During the period investigated, the mean basal circulating levels of calcitonin of both sexes were not significantly different between the two strains, although the Wag/Rij rats tended to have higher values. After a calcium challenge, the circulating calcitonin levels increased normally in the Wag/Rij strain as compared to Wistar rats of the same ages. Histological observations of their thyroids revealed a significant C cell hyperplasia, along with a weak immunostaining in some of the cells, due to a lack of secretory granules. Thus, in addition to the ability of developing C cell tumours on aging, the Wag/Rij strain is characterized by an early C cell hyperplasia leading to an increase of calcitonin secretion after a provocative secretion test.


Structural characterization of a novel KH-domain containing plant chloroplast endonuclease.
Chlamydomonas reinhardtii is a single celled alga that undergoes apoptosis in response to UV-C irradiation. UVI31+, a novel UV-inducible DNA endonuclease in C. reinhardtii, which normally localizes near cell wall and pyrenoid regions, gets redistributed into punctate foci within the whole chloroplast, away from the pyrenoid, upon UV-stress. Solution NMR structure of the first putative UV inducible endonuclease UVI31+ revealed an α1-β1-β2-α2-α3-β3 fold similar to BolA and type II KH-domain ubiquitous protein families. Three α-helices of UVI31+ constitute one side of the protein surface, which are packed to the other side, made of three-stranded β-sheet, with intervening hydrophobic residues. A twenty-three residues long polypeptide stretch (D54-H76) connecting β1 and β2 strands is found to be highly flexible. Interestingly, UVI31+ recognizes the DNA primarily through its β-sheet. We propose that the catalytic triad residues involving Ser114, His95 and Thr116 facilitate DNA endonuclease activity of UVI31+. Further, decreased endonuclease activity of the S114A mutant is consistent with the direct participation of Ser114 in the catalysis. This study provides the first structural description of a plant chloroplast endonuclease that is regulated by UV-stress response.


Developmental plasticity and maternal effects of reproductive characteristics in the frog, Bombina orientalis.
Life history theory suggests that reproductive characteristics such as ovum size and clutch size should be well buffered against vararies of the environment. However, studies which demonstrate environmental sensitivity of reproductive characteristics are increasing in number, as are studies which find that maternal effects are responsible for much of the variation in developmental and growth rates in embryonic and larval fish and amphibians. The data reported here demonstrate that the environment, in terms of temperature and food availability that a specific individual encounters during vitellogenesis, exerts a strong influence on both egg size and number. Warmer temperatures and less food decrease ovum size, while colder temperatures and less food decrease clutch size. The variation in ovum size that is induced by the environment can exert a strong influence on variation in offspring development and growth and serve as an excellent model for studies on the evolution of developmental plasticity.


Changes in sensory proteins in the bladder urothelium of patients with chronic kidney disease and end-stage renal disease.
Patients with chronic kidney disease (CKD) or end-stage renal disease (ESRD) frequently have lower urinary tract symptoms, such as frequency, urgency, or bladder pain. This study evaluated sensory protein expression in the bladder urothelium of patients with CKD or ESRD. Twenty-seven patients with ESRD or CKD and urodynamically proven detrusor underactivity (DU; n = 8) or bladder oversensitivity (n = 19) were enrolled in the study. These patients, and 10 controls, underwent cystoscopic biopsies of the urothelium. Western blotting analysis was used to examine the expression of sensory proteins, namely purinergic P2X3 , muscarinic M2 and M3 , and β3 -adrenergic (AR) receptors, as well as inducible (i) and epithelial (e) nitric oxide synthase (NOS), in tissue samples. Expression was compared between CKD or ESRD patients and controls. P2X3 receptor expression was lower, whereas β3 -AR was expression higher in the bladder urothelium of the patient group (ESRD and CKD combined) compared with controls. In addition, compared with controls, CKD patients had significantly lower P2X3 receptor expression, whereas ESRD patients had significantly higher M3 receptor expression. There were no significant differences in M2 receptor, eNOS, and iNOS expression between ESRD or CKD patients and controls. Patients with DU had significantly higher M2 and M3 receptor expression. There were no significant differences in the expression of any protein between ESRD and CKD patients, regardless of the presence of bladder pain or anuria. Significantly decreased P2X3 receptor and increased β3 -AR expression are seen in the bladder urothelium of patients with ESRD or CKD. The expression of these sensory proteins is not associated with decreased bladder capacity or anuria status in patients with ESRD or CKD.


Analysis of superiorly projecting anterior communicating artery aneurysms: anatomy, techniques, and outcome. A proposed classification system.
Superiorly projecting (SP) anterior communicating artery (AComA) aneurysms are typically described as a homogenous group. Clinically and microsurgically, these aneurysms vary in multiple important characteristics. We propose a microsurgical classification system for these complex aneurysms and review its implications regarding presentation, microsurgical techniques, and outcome. This retrospective analysis reviews patients undergoing clipping of SP AComA aneurysms (2005-2013). The classification system is based on the virtual plane created by the A2 segments and its relationship to the aneurysm. Aneurysm type was assessed by intraoperative images and videos. Type 1 is defined by bisection of the dome by the virtual plane. Type 2 is defined by dome projection posterior to this plane. Sagittal rotation of the plane defines type 3. We analyzed clinical presentation, morphology, angiographic characteristics, operative technique, and outcome relative to the classification types. There were 44 SP AComA aneurysms. 3D angiographic images predicted classification type in 83%. Type 1 presented more often with SAH (95.5%, p = 0.0046). There was no statistically significant difference between the types regarding patient demographics or aneurysm characteristics. In type 2, fenestrated clips were used frequently (87.5% p= 0.0016), and there was higher rate of intraoperative rupture (37.5%). Although there was no statistically significant difference between the types in respect to HH grade upon presentation, patients with type 2 aneurysms experienced higher rates of poor GOS (50%). The proposed classification system for SP AComA aneurysms has implications regarding surgical planning, micro-dissection, clipping, and outcome. Type 2 aneurysms carry significant surgical risk.


Distribution of cystinosin-LKG in human tissues.
Nephropathic cystinosis is multisystemic progressive disorder caused by mutations of CTNS gene that encodes for the lysosomal cystine co-transporter cystinosin, and for a less abundant isoform termed cystinosin-LKG, which is expressed in not only lysosomes but also other cell compartments. To overcome the absence of high-quality antibodies against cystinosin, we have obtained a rabbit antiserum against cystinosin-LKG and have analyzed in human tissues the expression of the two known cystinosin isoforms by RT-PCR, and the expression of cystinosin-LKG by immunohistochemistry. In most tissues, CTNS-LKG represents 5-20 % of CTNS transcripts, with the exception of the testis that expresses both isoforms in equal proportions. Cystinosin-LKG was found to be highly expressed in renal tubular cells, pancreatic islets of Langerhans, Leydig cells of the testis, mucoserous glands of the bronchial wall, melanocytes and keratinocytes. These results are parallel with many features of cystinosis, such as early onset Fanconi syndrome, male infertility, diabetes mellitus and hypopigmentation. Intermediate expression levels were of the LKG isoform observed in the gastro-intestinal tract and thyroid glands; low levels of expression were observed in the brain, skeletal and cardiac muscles.


Lateralized and frequency-dependent effects of prefrontal rTMS on regional cerebral blood flow.
Repetitive transcranial magnetic stimulation (rTMS) is a means to study the function and connectivity of brain areas. The present study addressed the question of hemispheric asymmetry of frontal regions and aimed to further understand the acute effects of high- and low-frequency rTMS on regional cerebral blood flow (rCBF). Sixteen healthy right-handed men were imaged using H(2)(15)O positron emission tomography (PET) immediately after stimulation. High (10 Hz)- and low (1 Hz)-frequency suprathreshold short-duration rTMS was applied over either the left or right dorsolateral prefrontal cortex (DLPFC). Slow and fast rTMS applied over the left DLPFC significantly increased CBF in the stimulated area. Compared to baseline, slow rTMS induced a significant increase in CBF contralateral to the stimulation site, in the right caudate body and in the anterior cingulum. Furthermore, slow rTMS decreased CBF in the orbitofrontal cortex (OFC, ipsilateral to stimulation side). Fast rTMS applied over the right DLPFC was associated with increased activity at the stimulation site, in the bilateral orbitofrontal cortex and in the left medial thalamus compared to 1-Hz rTMS. These results show that rCBF changes induced by prefrontal rTMS differ upon hemisphere stimulated and vary with stimulation frequency. These differential neurophysiological effects of short-train rTMS with respect to side and frequency suggest hemisphere-dependent functional circuits of frontal cortico-subcortical areas.


The participation of minorities in published pediatric research.
There is extensive documentation that minority adults are underrepresented in medical research, but there are scant data regarding minority children and their parents. All full-length articles published in three general pediatric journals between July 2002 through June 2003 were collected and reviewed. Articles were excluded if they did not include at least one U.S. researcher, all subjects enrolled at U.S. institutions, parents or children as subjects, some prospective data collection, or between eight and 10,000 subjects. Corresponding authors were surveyed to clarify race/ethnicity data, language barriers and how race/ethnicity data were collected. Two-hundred-twenty-eight articles qualified for further analysis. Black children and parents and Asian/Pacific Islander parents were overrepresented, and Hispanic children and parents were underrepresented compared to the Census data. Most researchers collected race/ethnicity data by having subjects self-report. Most studies did not have translation available, although most Hispanic and Asian/Pacific Islander subjects were enrolled in studies in which translation was available. Our data show that Hispanic and Asian/Pacific Islander research subjects are more likely to participate in pediatric research when translation is available. If the goal is to ensure access to pediatric research for all ethnic populations, then more research needs to accommodate non-English-speaking participants.


Uncovering the (un)attended: Pupil light responses index persistent biases of spatial attention in neglect.
Visuospatial neglect is a frequent and disabling disorder, mostly after stroke, that presents in impaired awareness to stimuli on one side of space. Neglect causes disability and functional dependence, even long after the injury. Improving measurements of the core attentional deficit might hold the key for better understanding of the condition and development of treatment. We present a rapid, pupillometry-based method that assesses automatic biases in (covert) attention, without requiring behavioral responses. We exploit the phenomenon that pupil light responses scale with the degree of covert attention to stimuli, and thereby reveal what draws (no) attention. Participants with left-sided neglect after right-sided lesions following stroke (n = 5), participants with hemianopia/quadrantanopia following stroke (n = 11), and controls (n = 22) were presented with two vertical bars, one of which was white and one of which was black, while fixating the center. We varied which brightness was left and right, respectively across trials. In line with the hypotheses, participants with neglect demonstrated biased pupil light responses to the brightness on the right side. Participants with hemianopia showed similar biases to intact parts of the visual field, whilst controls exhibited no bias. Together, this demonstrates that the pupil light response can reveal not only visual, but also attentional deficits. Strikingly, our pupillometry-based bias estimates were not in agreement with neuropsychological paper-and-pencil assessments conducted on the same day, but were with those administered in an earlier phase post-stroke. Potentially, we pick up on persistent biases in the covert attentional system that participants increasingly compensate for in classical neuropsychological tasks and everyday life. The here proposed method may not only find clinical application, but also advance theory and aid the development of successful restoration therapies by introducing a precise, longitudinally valid, and objective measurement that might not be affected by compensation.


Microhydration of Phenyl Formate: Gas-Phase Laser Spectroscopy, Microwave Spectroscopy, and Quantum Chemistry Calculations.
Herein, we have investigated the structure of phenyl formate⋅⋅⋅water (PhOF⋅⋅⋅H2 O) dimer and various non-covalent interactions present there using gas-phase laser spectroscopy and microwave spectroscopy combined with quantum chemistry calculations. Two conformers of PhOF⋅⋅⋅H2 O (C1 and T1), built on the two cis/trans conformers of the bare molecule, have been observed in the experiment. In cis-PhOF, there is an nCO → π A r * ${{{\rm \pi }}_{{\rm A}{\rm r}}^{{\rm {^\ast}}}}$ interaction between the lone-pair orbital of the carbonyl oxygen atom and the π* orbital of the phenyl ring, which persists in the monohydrated C1 conformer of PhOF⋅⋅⋅H2 O according to the NBO and NCI analyses. On the other hand, this interaction is absent in the trans-PhOF conformer as the C=O group is away from the phenyl ring. The C1 conformer is primarily stabilized by an interplay between O-H⋅⋅⋅O=C hydrogen bond and O-H⋅⋅⋅π interactions, while the stability of the T1 conformer is primarily governed by the O-H⋅⋅⋅O=C hydrogen bond. The most important finding of the present work is that the conformational preference of the PhOF monomer is retained in its monohydrated complex.


Discovering the value of nursing in high-technology environments: outcomes revisited.
The article argues that the current approach to specifying outcomes of nursing care in high-technology environments obscures rather than illuminates nursing's contributions to health care. Two nursing situations are used to illustrate a reframing of the idea of outcomes from the perspective and language of nursing as caring. Outcomes of nursing care are reconceptualized as value experienced within the nursing situation.


Confronting the Modern Gordian Knot of Urban Beekeeping.
With insect population declines, cities are important habitats for wild pollinators. Urban beekeeping is an increasingly popular activity, yet honeybees present important risks to wild insect pollinators in cities. We argue for new, scientifically evidenced urban pollinator strategies to simultaneously enhance the benefits of urban beekeeping while protecting wild pollinators.


Preoperative Pelvic Floor Muscle Exercise and Postprostatectomy Incontinence: A Systematic Review and Meta-analysis.
Preoperative pelvic floor muscle exercise (PFME) is often prescribed to reduce the severity of postprostatectomy incontinence. Systematic review and meta-analysis of evidence regarding the effect of preoperative PFME on postoperative urinary incontinence following radical prostatectomy. A systematic search was performed of the Cochrane Library, Medline, Embase, and all potential articles from references in relevant articles on 4 October 2014. We followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Identified reports were critically appraised for quality and relevance. Only studies of preoperative PFME compared with no preoperative PFME were included. Eleven studies were included based on the selection criteria. The total number of patients included in the final analysis was 739. In seven studies, sufficient quantitative data on postoperative incontinence were available for meta-analysis. At 1 mo, there was no difference in continence rates between the groups (odds ratio [OR]: 0.68; 95% confidence interval [CI], 0.45-1.03). At 3 mo, there was 36% improvement in the preoperative PFME group (OR: 0.64; 95% CI, 0.47-0.88). At 6 mo, there was no difference between groups (OR: 0.60; 95% CI, 0.32-1.15). When examining quality of life measures, four of seven studies demonstrated significant improvement in the preoperative PFME group at 3 mo, and two of these studies demonstrated significant differences at 6 mo. Preoperative PFME improves postoperative urinary incontinence after radical prostatectomy at 3 mo but not at 6 mo, suggesting it improves early continence but not long-term continence rates. We reviewed all evidence for preoperative pelvic floor muscle exercise (PFME) in treating urinary incontinence following radical prostatectomy. We found evidence to suggest that preoperative PFME improves early continence rates but not long-term continence rates.


Study of the expression of toll-like receptors in different histological types of colorectal polyps and their relationship with colorectal cancer.
Dysregulation of toll-like receptors (TLR) signaling can result in chronic inflammatory and over-exuberant repair responses. The aim of this study was to investigate the expression and clinical relevance of TLR in colorectal polyps. The expression levels of six TLR were analyzed in 70 patients with different histological types of colorectal polyps, 38 of which developed colorectal carcinoma (CC). These analyses were performed by real-time polymerase chain reaction, western blot, and immunohistochemistry. TLR9 expression was higher in hyperplastic or adenomatous polyps compared to other polyp types. Hyperplastic polyps also showed increased TLR7 levels compared to the other polyp types. TLR7 expression was lower in both hyperplastic and tubulovillous adenoma polyps from patients who developed CC. TLR9 expression was decreased in hyperplastic and villous polyps from patients who developed CC. Our findings suggest a possible protective role of TLR expression against malignant transformation in the colorectal mucosa. TLR may represent a pathological marker of CC risk in colorectal polyps. The role of these factors in the pathology of colorectal polyps deserves further investigation.


Sexual and reproductive health knowledge among adolescents in eight sites across sub-Saharan Africa.
To examine knowledge of menstruation, HIV and STIs other than HIV across eight sites in SSA to develop effective programmatic interventions enabling adolescents to achieve positive SRH as their transition to adulthood. We combine data from eight Health and Demographic Surveillance Sites across sub-Saharan Africa, from an adolescent-specific survey that included 7116 males and females age 10-19 years old. We provide pooled and site-specific estimates from multiple analytic models examining the how year-specific age, school attendance and work correlate with knowledge of menstruation, HIV knowledge and knowledge of sexually transmitted infections (STIs) other than HIV. Many adolescents lack knowledge of menstruation (37.3%, 95% CI 31.8, 43.1 do not know of menstruation) and STIs other than HIV (55.9%, 95% CI 50.4, 61.3 do not know of other STIs). In multivariate analysis, older age, being in school and wealth are significant positive correlates of STI knowledge. Older adolescent age, female sex and being in school are significant positive correlates of knowledge of menstruation. Knowledge of HIV is high (89.7%, 95% CI 8.3, 12.7 know of HIV) and relatively similar across adolescent age, sex, wealth and school and work attendance. Knowledge of HIV is widespread across adolescents in these communities in sub-Saharan Africa, but knowledge of other dimensions of sexual and reproductive health - menstruation and other STIs in this study - is lacking especially for early adolescents (10- to 14-year olds). The dissemination of more comprehensive sexual and reproductive health information is needed within these and similar communities in SSA to help adolescents gain insight on how to make their own decisions towards positive adolescent sexual and reproductive health and protect them from risks.


Detection of amyloid beta protein precursor immunoreactivity in normal and Alzheimer's disease cerebrospinal fluid.
The amyloid A4 (or beta protein), a 4.2 kD polypeptide, is a major component of amyloid deposits in the brains of patients with Alzheimer's Disease (AD). The self-aggregating amyloid A4 protein of AD is encoded as part of three larger proteins by the amyloid A4 precursor gene. The corresponding proteins have 695, 751 and 770 amino acid residues. To investigate the utility of amyloid beta protein precursor (A beta PP) as a diagnostic marker for AD an antiserum against a synthetic peptide (175-186), predicted from cDNA sequence for A beta PP, was used. The immunoreactivity of A beta PP in normal and AD cerebrospinal fluid (CSF) was measured by Western blot and detected with radiolabeled protein A. A total of fifty-seven CSF samples (AD = 27 and normal = 30) were analyzed for A beta PP immunoreactivity. A polyclonal antibody detected two major protein bands with apparent molecular weights of 105kD and 90kD both in normal and AD CSF. The difference between normal and AD CSF was not significant. These results indicate that immunoreactivity of A beta PP is present both in normal and AD CSF, and that the difference is too small to be used as a diagnostic marker.


Risk factors for patients with acute hospital-acquired symptomatic pulmonary thromboembolism.
This study aimed to identify independent risk factors for acute hospital-acquired symptomatic pulmonary embolism (HA-SPE) by comparing the clinical data of HA-SPE and acute nonhospital-acquired symptomatic pulmonary embolism (NHA-SPE). A total of 292 patients were included in the analysis and divided into two groups: 191 patients had acute NHA-SPE, and 101 patients had acute HA-SPE. The average age of these 292 patients was 63.2 years, and the sample included 145 males. Multivariate analysis showed that malignant tumour (OR, 3.811; 95% CI [1.914-7.586], P = 0.000), recent surgery (OR, 7.310; 95% CI 3.392-15.755], P = 0.000), previous VTE (OR, 5.973; 95% CI 2.194 16.262], P = 0. 000), and the length of stay (LOS) (OR, 1.075; 95% CI [1.040-1.111], P = 0.000) were independent risk factors for acute HA-AEP. The c-statistic for this model was 0.758 (95% CI [0.698-0.800], P < 0.0001). The K-M curve showed that the hazard ratio (HR) of the HA group to the NHA group in all-cause mortality was 3.807 (95% CI [1.987, 7.295], P = 0.0061). Strengthening the prevention and control of patients with these risk factors may reduce the incidence of acute HA-SPE.


Obesity and SARS-CoV-2: Considerations on bariatric surgery and recommendations for the start of surgical activity.
The SARS-CoV-2 pandemic has a great impact worldwide, being Spain one of the most affected countries. The delay in bariatric surgery can have fatal consequences since up to 50% of the patients who are on the waiting list develop a new comorbidity during the time they remain on it and 1.5% of patients die while waiting for the intervention. That is why bariatric surgery should not be delayed, if the occupation of the hospital by COVID-19+ patients decreases significantly, and sufficient resources and safety are available to restart surgery in patients with benign pathology. This document contains the main recommendations for the bariatric surgery programs in our country from the point of view of safety, bariatric patient preparation and follow up during the SARS-CoV-2 pandemia.


Clinical characteristics of Demodex-associated recurrent hordeola: an observational, comparative study.
Our study evaluated the association between Demodex infestation and recurrent hordeola and examined the clinical features associated with these eyelid lesions. This was an observational, comparative study. We reviewed 250 patients and divided them into the recurrent hordeolum (n = 153) and control (n = 97) groups. Demodex infestation was detected by epilating eyelashes around the lesion/s and viewing them under a light microscope. Patient medical records and photographs were retrospectively analyzed to identify the clinical characteristics of Demodex-associated recurrent hordeola. Demodex was detected in 91 (59.5%) and 17 (17.5%) patients in the recurrent hordeolum and control groups (p < 0.001), respectively. In the recurrent hordeolum group, Demodex mites were found in 74 (68.5%) and 17 (37.8%) of the adult and pediatric patients (p < 0.001), respectively. Among patients with recurrent hordeola, patients in their 20s were most likely to have concomitant Demodex infestation. Patients with Demodex infestations were also more likely to develop recurrent lesions within a shorter period of time from the primary incision and curettage. The most common presentation of Demodex-associated recurrent lesions was external hordeola (67%) (p = 0.002). Demodex infestation may cause recurrent hordeola in adults and children. These mites may play a greater role in the development of lesions in adult patients. The strongest association between Demodex infestation and recurrent lesions was seen in patients in their 20s. Our results suggest that if the hordeola recur within a short period of time with the clinical characteristics of external location of eyelid, multiple numbers of lesions, or anterior blepharitis, eyelash epilation should be performed to identify the presence of Demodex mites.


Tibio-talo-calcaneal arthrodesis with retrograde compression intramedullary nail fixation for salvage of failed total ankle replacement: a systematic review.
Failed total ankle replacement is a complex problem that should only be treated by experienced foot and ankle surgeons. Significant bone loss can preclude revision total ankle replacement and obligate revision though a complex tibio-talo-calcaneal arthrodesis. A systematic review of the world literature reveals a nonunion rate of 24.2%. A weighted mean of modified American Orthopaedic Foot and Ankle Society Ankle and Hindfoot Scale demonstrated fair patient outcomes of 58.1 points on an 86-point scale (67.6 points on a 100-point scale). Complications were observed in 38 of 62 (62.3%) patients reviewed, with the most common complication being nonunion.


Fluorogenic substrates with single fluorophores for nucleic acid-modifying enzymes: design principles and new applications.
Nucleic acid-modifying enzymes are widely used in numerous applications. Many of these proteins are also important drug targets. Thus, better assays for the evaluation of their activities are always needed and are continuously being developed. Recently, I reported on a set of assays for several DNA-modifying enzymes (polymerases, endonucleases, and ligase) based on simple, hairpin-type oligonucleotide substrates labeled with a single fluorophore (Anal. Biochem. 412 (2011) 229-236). The present paper reports further studies on the mechanism of action of these substrates. It was assumed that the single fluorophore of these substrates is substantially quenched by stacking onto the terminal base(s) of the duplex, and that any perturbation of that stacking causes an increase in fluorescence. Based on this assumption, substrates of the same type for a variety of additional enzymes were developed and tested. The new assays described herein are for T4 polynucleotide kinase, the DNA repair enzymes uracil-DNA glycosylase (UDG) and formamido-pyrimidine-DNA glycosylase (FPG), 3'-5' exonucleases, and enzymes with template-independent terminal transferase activity such as Taq polymerase. All of these molecules are easy to synthesize, and similar substrates for other enzymes can rapidly be designed based on the principles outlined in this work.


Insulin signaling meets vesicle traffic of GLUT4 at a plasma-membrane-activated fusion step.
A hypothesis that accounts for most of the available literature on insulin-stimulated GLUT4 translocation is that insulin action controls the access of GLUT4 vesicles to a constitutively active plasma-membrane fusion process. However, using an in vitro fusion assay, we show here that fusion is not constitutively active. Instead, the rate of fusion activity is stimulated 8-fold by insulin. Both the magnitude and time course of stimulated in vitro fusion recapitulate the cellular insulin response. Fusion is cell cytoplasm and SNARE dependent but does not require cell cytoskeleton. Furthermore, insulin activation of the plasma-membrane fraction of the fusion reaction is the essential step in regulation. Akt from the cytoplasm fraction is required for fusion. However, the participation of Akt in the stimulation of in vitro fusion is dependent on its in vitro recruitment onto the insulin-activated plasma membrane.


Enhancing enzymatic saccharification of sunflower straw through optimal tartaric acid hydrothermal pretreatment.
Sunflower straw, a usually neglected and abundant agricultural waste, has great potential for contributing to environmental protection realizing its high-value of valorization if utilizing properly. Because hemicellulose contains amorphous polysaccharide chains, relatively mild organic acid pretreatment can effectively reduce its resistance. Through hydrothermal pretreatment, sunflower straw was pretreated in tartaric acid (1 wt%) at 180 °C for 60 min to enhance its reducing sugar recovery. After tartaric acid-assisted hydrothermal pretreatment, 39.9% of lignin and 90.2% of xylan were eliminated. The reducing sugar recovery increased threefold, while the solution could be effectively reused for four cycles. The properties of more porous surface, improved accessibility, and decreased surface lignin area of sunflower straw were observed through various characterizations, which explained the improved saccharide recovery and provided a basis for the mechanism of tartaric acid-assisted hydrothermal pretreatment. Overall, this tartaric acid hydrothermal pretreatment strategy greatly provided new impetus for the biomass refinery.


Multicenter, randomized trial for stage IIIB or IV non-small-cell lung cancer using weekly paclitaxel and carboplatin followed by maintenance weekly paclitaxel or observation.
To explore the efficacy and safety of three regimens of weekly paclitaxel plus carboplatin as initial therapy and the feasibility of subsequent maintenance therapy versus observation in patients with advanced non-small-cell lung cancer (NSCLC). Four hundred one patients were randomly assigned to one of the following arms: arm 1, paclitaxel 100 mg/m2 weekly for 3 of 4 weeks with carboplatin (area under the curve [AUC] = 6) on day 1; arm 2, paclitaxel 100 mg/m2 and carboplatin (AUC = 2) weekly for 3 of 4 weeks; or arm 3, paclitaxel 150 mg/m2 cycle 1 and 100 mg/m2 cycle 2 and carboplatin (AUC = 2) weekly for 6 of 8 weeks. Patients who responded (n = 130) at week 16 were randomly assigned to either weekly paclitaxel therapy (70 mg/m2, 3 of 4 weeks; n = 65) or observation (n = 65). For the 390 assessable patients, the objective response rates observed with initial therapy were 32% for arm 1, 24% for arm 2, and 18% for arm 3. The median time to progression and median survival times were 30 and 49 weeks for arm 1, 21 and 31 weeks for arm 2, and 27 and 40 weeks for arm 3, respectively. The 1-year survival rates were 47% for arm 1, 31% for arm 2, and 41% for arm 3. Arm 1, paclitaxel 100 mg/m2 weekly for 3 of 4 weeks with carboplatin (AUC = 6) administered on day 1, demonstrates the most favorable therapeutic index in patients with advanced NSCLC.


Angiotensin II and epidermal growth factor receptor cross-talk mediated by a disintegrin and metalloprotease accelerates tumor cell proliferation of hepatocellular carcinoma cell lines.
The cross-talk pathway between angiotensin II (AngII) and the epidermal growth factor receptor (EGFR) mediated by epidermal growth factor (EGF)-like ligands cleaved by a disintegrin and metalloprotease (ADAM) has been elucidated in several cell types. Even though the liver is a representative angiotensinogen-producing organ, such cross-talk has never been elucidated in hepatocellular carcinomas (HCCs). We investigated whether AngII exerted a mitogenic effect on HCC cell lines through the AngII-EGFR cross-talk pathway. We determined the expression and/or phosphorylation status of AngII receptor type 1 (AGTR1), ADAM9, ADAM17, ERK1/2, STAT3, AKT and EGFR in five HCC cell lines using Western blotting. Proliferation and invasion activities were measured by ATP and Matrigel invasion assays, respectively. AGTR1 was expressed ubiquitously in HCC cell lines. EGFR expression in HepG2 was relatively weaker than that in the remaining HCC cell lines. The phosphorylation status of EGFR, ERK1/2, STAT3 and AKT was upregulated by AngII treatment in two EGFR-overexpressing cell lines (Huh7 and PLC/PRF/5), but not in HepG2 (showing weak EGFR expression). AngII stimulation significantly accelerated proliferation and invasion activities in Huh7 and PLC/PRF/5, and was inhibited by pretreatment with an ADAM inhibitor. A selective AGTR1 blocker significantly repressed proliferation activity in both cell lines, but did not significantly repress the invasion activity. Both chemical agents and neutralizing antibodies against ADAMs (ADAM9 and ADAM17) and EGF-like ligands suppressed EGFR transactivation and/or subsequent phosphorylation of ERK1/2, STAT3 and AKT. These results suggest that AngII-EGFR cross-talk signaling mediated by ADAMs is involved in the proliferation and invasion activities of several HCC cell lines.


Toxicological safety evaluation of the cultivated Chinese cordyceps.
The Chinese cordyceps, a parasitic Thitarodes insect-Ophiocordyceps sinensis fungus complex in the Qinghai-Tibet Plateau, is one of the most valuable traditional Chinese medicines and health food for ameliorating conditions associated with aging and for treating fatigue, night sweats, hyperglycemia, hyperlipidemia, respiratory, renal and liver diseases, and hyposexuality. The natural Chinese cordyceps resource is rare due to its harsh growing environment, limited geographical distribution and global climate warming. Artificial cultivation of Chinese cordyceps has been successfully established to meet its high demand in market. The present study aims to evaluate the toxicological safety of the cultivated Chinese cordyceps and provide scientific data for subsequent development and utilization of this valuable biological resource. The Chinese cordyceps was cultivated by mimicking the habitat environment in low-altitude areas and identified by morphological and microscopic characteristics. Its phytochemical profile was determined by the HPLC. Toxicological studies based on the cultivated Chinese cordyceps were conducted, including chromosomal aberration test of Chinese hamster lung (CHL) cells, Ames test, acute toxicity test and micronucleus (MN) test of bone marrow cells. The Chinese cordyceps successfully cultivated in low-altitude areas exhibited the same morphological and microscopic characteristics as natural Chinese cordyceps. The adenosine content was in accordance with the Chinese Pharmacopoeia (2015 Edition). The HPLC fingerprint was determined and five main chromatographic peaks representing uracil, uridine, inosine, guanosine and adenosine were identified. No dose-dependent increase in the rates of chromosomal aberration was detected in the presence or absence of metabolic activation system. Ames test also demonstrated no dose-dependent increase in the number of reversion mutation for five bacterial strains, with or without rat liver microsomal enzyme mixture (S9) metabolic activation, at a quantity range of 128-5000 μg cultivated Chinese cordyceps per plate. The acute toxicity test with mice showed that after 20 g/kg oral administration of cultivated Chinese cordyceps, neither animal death nor any abnormal change in general dissection of various tissues and organs of the animals were found within 14 days. The median lethal dose (LD50) was greater than 5 g/kg, which is regarded as a non-toxic level, and maximum tolerable dose (MTD) of cultivated Chinese cordyceps in ICR mice was more than 20 g/kg. MN test of mouse bone marrow cells indicated no significant differences among each sample dose and the negative control. Based on the results from four toxicological tests, it was concluded that the cultivated Chinese cordyceps was classified as non-toxic in one single administration at high doses by intragastric route in mice. This study provides scientific experimental basis for its safety.


Increasing numbers at a specialist coeliac clinic: contribution of serological testing in primary care.
Serological testing, using IgA class endomysial and tissue transglutaminase antibodies has high sensitivity and specificity for coeliac disease and allows case finding by clinicians other than gastroenterologists. We reviewed new coeliac patients seen over a 9-year period to determine how the availability of serology, particularly to primary care physicians, has changed rates and sources of diagnosis. Files of patients attending a specialist coeliac clinic who were diagnosed from 1996 through 2004 were reviewed. Patients with villous atrophy consistent with gluten sensitive enteropathy (Marsh III) on duodenal biopsy were selected. Data analysed included clinical characteristics, endomysial and tissue transglutaminase antibodies status and source of request for serology. Over the study period 347 new coeliac patients, comprising adults and children aged 10 years and over, were identified, of whom 163 (47%) were identified by serological testing in primary care, 152 (44%) at the hospital gastroenterology department and 32 (9%) by other physicians in secondary care. Over three consecutive 3-year periods, the percentage of patients identified in primary care rose from 28% through 47% to 60%, with a rise in total numbers diagnosed from 93 through 118 to 136. There was no change in patient clinical characteristics over the study period. Though tissue transglutaminase antibodies were less sensitive than endomysial antibodies, combined testing obtained a sensitivity of over 90%. Patients identified in primary care were significantly younger and more likely to present with diarrhoea as a primary symptom. Currently over half of our coeliac patients are identified by serological testing in primary care, which has resulted in an overall rise in diagnosis rates. Primary care practitioners have an important role in the diagnosis of coeliac disease, particularly of patients who present with non-gastrointestinal symptoms. The contribution of specialists other than gastroenterologists in secondary care is disappointing and may improve with directed education.


Challenges in the design of insulin and relaxin/insulin-like peptide mimetics.
Peptidomimetics are designed to overcome the poor pharmacokinetics and pharmacodynamics associated with the native peptide or protein on which they are based. The design of peptidomimetics starts from developing structure-activity relationships of the native ligand-target pair that identify the key residues that are responsible for the biological effect of the native peptide or protein. Then minimization of the structure and introduction of constraints are applied to create the core active site that can interact with the target with high affinity and selectivity. Developing peptidomimetics is not trivial and often challenging, particularly when peptides' interaction mechanism with their target is complex. This review will discuss the challenges of developing peptidomimetics of therapeutically important insulin superfamily peptides, particularly those which have two chains (A and B) and three disulfide bonds and whose receptors are known, namely insulin, H2 relaxin, H3 relaxin, INSL3 and INSL5.


Demonstration of a two-domain structure of antithrombin III during its denaturation in guanidinium chloride.
The denaturation of human antithrombin III in urea and guanidinium chloride (GdmCl) was investigated by intrinsic fluorescence, circular dichroism, and absorption difference spectroscopy. Results suggest the existence of two structural domains as evidenced by the occurrence of two structural transitions, one at 0.7 M GdmCl and the other at 2.3 M GdmCl. This multistate unfolding transition has been confirmed under various protein concentrations and incubation times using different antithrombin III preparations, including a preparation that had been heated at 60 degrees C in the presence of 0.5 M citrate. The persistence of the multistate transition under these conditions rules out the possibilities that it could be due to the presence of different antithrombin populations in a mixture or the presence of a prosthetic group in the molecule. The first unfolding domain (0.7 M GdmCl) is stabilized by heparin and citrate. These protections suggest that the first unfolding domain of low stability may have functional relevance and important implications with respect to antithrombin III-heparin and antithrombin III-protease interaction.


Wavelength of light and photophobia in inherited retinal dystrophy.
Inherited retinal dystrophy (IRD) patients often experience photophobia. However, its mechanism has not been elucidated. This study aimed to investigate the main wavelength of light causing photophobia in IRD and difference among patients with different phenotypes. Forty-seven retinitis pigmentosa (RP) and 22 cone-rod dystrophy (CRD) patients were prospectively recruited. We designed two tinted glasses: short wavelength filtering (SWF) glasses and middle wavelength filtering (MWF) glasses. We classified photophobia into three types: (A) white out, (B) bright glare, and (C) ocular pain. Patients were asked to assign scores between one (not at all) and five (totally applicable) for each symptom with and without glasses. In patients with RP, photophobia was better relieved with SWF glasses {"white out" (p < 0.01) and "ocular pain" (p = 0.013)}. In CRD patients, there was no significant difference in the improvement wearing two glasses (p = 0.247-1.0). All RP patients who preferred MWF glasses had Bull's eye maculopathy. Meanwhile, only 15% of patients who preferred SWF glasses had the finding (p < 0.001). Photophobia is primarily caused by short wavelength light in many patients with IRD. However, the wavelength responsible for photophobia vary depending on the disease and probably vary according to the pathological condition.


Organisation and origin of a B chromosome centromeric sequence from Brachycome dichromosomatica.
Brachycome dichromosomatica is an Australian native daisy that has two pairs of A chromosomes and up to three B chromosomes in some populations. A putative B-specific tandem repeat DNA sequence (Bd49) was isolated previously. Here we describe further characterisation of this sequence and investigate its possible origin. Southern analysis showed that all individual B chromosomes examined have highly methylated tandem repeats of Bd49 but differences in banding pattern for distinct B isolates suggested that the sequence is in a state of flux. Using in situ hybridisation, the sequence was shown to be located at the centromeric region of the B chromosome. Southern analysis of genomic DNA with Bd49 demonstrated that multiple copies of the sequence exist in the genomes of B. eriogona, B. ciliaris, B. segmentosa and B. multifida (none of which have B chromosomes) whereas other species tested (including 0B plants of B. dichromosomatica and 0B and +B B. curvicarpa and B. dentata) have few or no copies. Genomic clones and Bd49-like sequences derived by the polymerase chain reaction (PCR) were obtained from five species but determination of phylogenetic relationships within the genus and inference as to the possible origin of the B chromosome were problematic because of extensive intragenomic heterogeneity of the sequences.


Insulin resistance in total lipodystrophy: evidence for a pre-receptor defect in insulin action.
The cause of insulin resistance in lipodystrophic diabetes is unknown but has generally been ascribed to dysfunction at either the receptor or post receptor level. In a 14 year-old girl with total acquired lipodystrophy, subcutaneous and intravenous insulin requirements approximated 600 units daily. However, circulating total and free insulin levels were not increased, and during testing by the euglycemic clamp method, the glucose response to increasing free insulin concentrations was within the range found in eight subjects with insulin-dependent diabetes. Insulin clearance during the euglycemic clamp was 43, 98, 115, and 116 mL/kg/min at each of four insulin infusion rates compared to means of 13, 13, 12, and 11 in the control subjects with diabetes. No detectable degrading activity was present in serum, and serum inhibited insulin degradation normally. Binding of insulin to IgG, IgM, and IgE was not increased, insulin binding to monocytes and erythrocytes was not sufficiently abnormal to account for the the insulin resistance, and insulin receptor increased insulin clearance or accelerated degradation of insulin by tissues.


Fetal echocardiography: factors that influence imaging of the fetal heart during the second trimester of pregnancy.
The four-chamber view of the heart is an important component of the ultrasonographic examination of the fetus. However, during the second trimester of pregnancy the fetal heart cannot always be imaged in every patient. The purpose of this study was to ascertain the rate of successful imaging of the fetal heart during the second trimester and to determine factors that may influence imaging. Seven hundred and nine second trimester fetuses were examined and an attempt was made to obtain the four-chamber and outflow tract views of the heart. Analysis included multiple logistic regression models of the main effects and interactions of ten candidate variables. The four chambers and outflow tracts were imaged in 643 fetuses (90.7%) and not imaged in 66 (9.3%). Fifty-two of 709 patients (7.3%) had had previous surgery. In the 52 patients with a history of previous surgery, the heart could not be imaged in 18 (34%). Six hundred and fifty-seven patients (92.7%) did not have previous surgery. Of this group, the fetal heart could not be imaged in 48 (7.3%). In only one fetus in which the heart could not be imaged was it because of fetal position. Three independent risk factors that influenced imaging of the fetal heart were gestational age, maternal adipose tissue thickness, and previous lower abdominal surgery. Increasing gestational age increased the probability of imaging the heart, whereas increasing adipose tissue thickness and a history of previous surgery decreased the probability of imaging the heart. When the fetal heart cannot be imaged during the second trimester, these factors should be identified. Using data from this study, the gestational age at which the highest probability of imaging the heart can be determined if the thickness of the adipose tissue and a history of lower abdominal surgery are known.


Insulin-glycerolipid mediators and gene expression.
Insulin is an anabolic polypeptide hormone with pleiotrophic effects. During the decades since the initial description by Banting and Best, the acute effects of insulin have been widely studied with particular focus on the mechanism or mechanisms of insulin activation of hexose transport and regulation of metabolic enzyme activity. However, recently there has been a major expansion of investigation to include insulin regulation of gene expression with multiple insulin-sensitive specific mRNAs now reported. In this review, we explore the involvement of insulin-induced changes in plasma membrane glycerolipid metabolism in the transmembrane signaling process required for insulin regulation of mRNA levels. Insulin increases diacylglycerol levels in insulin-responsive cells, and synthetic diacylglycerols or their phorbol ester diacylglycerol analogs, such as 4 beta,9 alpha,12 beta,13 alpha, 20-pentahydroxytiglia-1,6-dien-3-one 12 beta-myristate 13-acetate (TPA), mimic insulin regulation of ornithine decarboxylase mRNA, c-fos mRNA, and phosphoenolpyruvate carboxykinase mRNA levels. This suggests that insulin regulation of specific mRNA levels may be mediated by insulin-induced changes in phospholipid metabolism and that diacylglycerol may play a pivotal role in insulin regulation of gene expression.


Prediction of toxicity using quantitative structure-activity relationships.
The relationships between toxicity and physicochemical indices of derivates of four chemical groups: of phenol, benzene, aniline and aliphatic amine were studied. Using the Hansch model the feasibility of using the octanol/water partition coefficient, electronic and steric constants was estimated. The acute lethal doses and no effect levels for rats were found not to be predictable using these parameters. The molecular connectivity indices, which describe the topology of the molecular structure have shown a closer relationship to toxicity, than the physicochemical parameters. The application of both physicochemical and molecular connectivity indices provided the best correlations and has been recommended for prediction of toxicological parameters.


catena-Poly[[(8-amino-quinoline-κN,N')cadmium]-di-μ-thio-cyanato-κN:S;κS:N-[(8-amino-quinoline-κN,N')cadmium]-di-μ-chlorido].
In the title compound, [CdCl(NCS)(C(9)H(8)N(2))](n), the Cd(II) atom is in a distorted octa-hedral coordination environment defined by two chloride anions, two N atoms from an 8-amino-quinoline ligand, one N atom from one thio-cyanate anion and one S atom from a symmetry-related thio-cyanate anion. Two Cd(II) atoms are bridged by two chloride anions, forming an inversion-related Cd(2)Cl(2) unit; these units are further linked through thio-cyanate anions, leading to a chain structure extending parallel to [010]. Weak π-π stacking inter-actions with centroid-centroid distances of 3.430 (4) Å and an inter-planar separation of 3.390 (3) Å between the pyridine and benzene rings link the chains into a two-dimensional network parallel to (10[Formula: see text]). Weak inter-molecular C-H⋯Cl hydrogen-bonding inter-actions help to consolidate the crystal packing.


Psychological aspects of people with headache undergoing percutaneous electrostimulation: preliminary data.
Percutaneous electrostimulation is performed in the treatment of headaches taking into account, after preliminary tests, the relative psychological symptom connected to headache. The authors suggest that a preliminary analysis is indispensable to the treatment of psychodynamic and psychopathologic mechanisms connected to headache.


Quantitative ultrasound criteria for risk stratification in clinical practice: a comparative assessment.
This study aimed to compare two different classifications of the risk of fracture/osteoporosis (OP) based on quantitative ultrasound (QUS). Analyses were based on data from the Epidemiological Study on the Prevalence of Osteoporosis, a cross-sectional study conducted in 2000 aimed at assessing the risk of OP in a representative sample of the Italian population. Subjects were classified into 5 groups considering the cross-classification found in previous studies; logistic regression models were defined separately for women and men to study the fracture risk attributable to groups defined by the cross-classification, adjusting for traditional risk factors. Eight-thousand six-hundred eighty-one subjects were considered in the analyses. Logistic regression models revealed that the two classifications seem to be able to identify a common core of individuals at low and at high risk of fractures, and the importance of a multidimensional assessment in older patients to evaluate clinical risk factors together with a simple, inexpensive, radiation-free device such as QUS.


Nonlinear imaging and vibrational spectroscopic analysis of cellulosic fibres treated with COEX® flame-retardant for tapestry preservation.
Cellulose-based fabrics are widely used in the preservation and storage of historic tapestries. Their ease of flammability is a serious concern that greatly limits their applications and requires the development of effective and safe flame-retardant treatments. In this work, we analysed linen and cotton textile samples before and after COEX® treatment, a patented green technology imparting anti-flame properties by functionalizing the cellulose molecules with phosphorus and sulphur groups. Some of the samples were also exposed to photo-induced ageing after the treatment. The resulting structural and chemical changes in both fibres were characterized by nonlinear optical imaging modalities, namely Second Harmonic Generation (SHG) and Two-Photon Excited Fluorescence microscopies (TPEF), and Raman and Attenuated Total Reflection - Fourier Transform Infrared (ATR-FTIR) spectroscopies. Complementary results evidenced a reduction in microfibril crystallinity, attributed mainly to the reduction of hydrogen bonding among cellulose macromolecules, with a concomitant increase in fluorescence possibly due to the introduction of ester groups into cellulose chains and to decomposition of lignin into fluorescent by-products.


Quantitative high-performance liquid chromatography-tandem mass spectrometry method for the analysis of free desmosines in plasma and urine.
A rapid method for the determination of the sum of free desmosine and isodesmosine in human plasma and urine is described. Efficient sample clean-up prior to LC-MS/MS analysis is mandatory for detection of free desmosines in plasma samples. The combination of ultra-filtration and a two-step solid phase extraction minimizes the sample complexity and ion suppression effects. The flow through from the ultra filtration is passed through a C18 resin and then the target analytes are trapped and enriched on a mixed mode solid phase extraction material. The combination of these three orthogonal sample preparation steps allows detection of endogenous free desmosines in plasma from healthy individuals. An analytical column packed with porous graphitic carbon material enables the retention of the polar desmosine analytes, which are measured by electrospray ionization tandem mass spectrometry. Deuterium labeled isodesmosine is added as internal standard and a linear calibration curve was constructed in the range of 0.1-2.0 nmol/L for plasma samples and 5-200 nmol/L for urine samples. These results demonstrate that the described LC-MS/MS method provides sensitive, repeatable and accurate quantification of free desmosines in plasma and urine samples.


Primary malignant liver tumors in children.
Liver tumors constitute only 1-4% of all solid tumors in children. Two-thirds of these are malignant. The primary malignant tumors are hepatoblastoma (HB), hepatocellular carcinoma (HCC), rhabdomyosarcoma (RMS), angiosarcoma, rhabdoid tumor, undifferentiated sarcoma and other rarer tumors. Of these HB is the commonest. The diagnosis of HB is based on the radiology, elevated levels of α-fetoprotein (αFP) and the histology/cytology. Staging is essential for risk categorization, risk adapted treatment and prognostication. The commonest staging and risk categorization system used today is PRETEXT system that is being used by nearly all multicentre trials (American, European, German, Japanese) in some way. Treatment of HB is multimodal with surgery and chemotherapy being the main modalities. Survival is not possible without complete surgical resection. Majority of tumors are unresectable at presentation but can be made resectable with chemotherapy, giving a resection rate of more than 85%. Cisplatin is the main stay of chemotherapy and is a part of all multidrug protocols. The 3-y overall survival (OS) today stands at 62%-70% but only 25% patients with metastasis get cured. Panhepatic tumors and those with local factors causing unresectability are now dealt with liver transplantation which has also given a survival rate of nearly 85%. The overall management of HB and HCC has evolved over the past 3 decades giving good long term survival rates for HB, though patients with HCC still do poorly. Successive therapeutic trials have focused attention on increasing the efficiency and reducing the toxicity and long term side effects of the treatment. Among the other uncommon tumors the rhabdoid tumor and angiosarcoma are chemoresistant and have a poor outcome while the undifferentiated sarcoma and rhabdomyosarcoma are now showing better response to the currently used chemotherapy combinations.


Evidence-based criteria for pain of interstitial cystitis/painful bladder syndrome in women.
No diagnostic physical signs, urologic findings, or laboratory tests are available for interstitial cystitis/painful bladder syndrome (IC/PBS). Its diagnosis is determined by symptoms and the exclusion of mimicking diseases. We hypothesized that certain pain characteristics are sensitive criteria for diagnosing IC/PBS. In women with recent-onset IC/PBS recruited in 2004 to 2006 for the case-control study, "Events Preceding Interstitial Cystitis," we identified the locations of each patient's pain and in a nonleading way asked about the effects of 17 different experiences (criteria) on the pain. We identified a set of criteria that described the largest number of patients in the Events Preceding Interstitial Cystitis study. In a secondary analysis of another cohort recruited by others in 1993 to 1997, the Interstitial Cystitis Database, we determined the proportion of patients captured by these same criteria. In the Events Preceding Interstitial Cystitis study, pain that worsened with a certain food or drink and/or worsened with bladder filling and/or improved with urination was reported by 151 (97%) of 156 patients. These were the only three criteria that applied directly to the bladder. The same three criteria described the pain of 262 (97%) of 270 women in the Interstitial Cystitis Database who "definitely" had IC/PBS. An hypothesis generated in one IC/PBS patient group and tested in another--pain that worsened with certain food or drink and/or worsened with bladder filling and/or improved with urination--was described by 97% of the patients with IC/PBS in each cohort. This triad might describe the pain of IC/PBS and contribute to a sensitive case definition. Estimating specificity awaits comparison with other diseases with similar symptoms.


Deacylated lipopolysaccharide inhibits plasminogen activator inhibitor-1, prostacyclin, and prostaglandin E2 induction by lipopolysaccharide but not by tumor necrosis factor-alpha.
Bacterial LPS and TNF induce vascular endothelial cells to express a variety of response molecules. LPS that is partially deacylated (dLPS) by a human neutrophil enzyme blocks the ability of LPS, but not TNF, to augment one of these responses, the expression of endothelial cell surface molecules that promote neutrophil adherence (J. Exp. Med. 1987; 165:1393-1402). We show that dLPS can inhibit the ability of LPS, but not TNF, to elicit the expression of plasminogen activator inhibitor-1 (PAI-1), prostacyclin, and PGE2 by human umbilical vein endothelial cells. dLPS also prevented the accumulation of specific PAI-1 mRNA in response to LPS, but not to TNF. Neither the LPS- or TNF-induced expression of PAI-1 nor the dLPS inhibition of the LPS response was mediated by prostanoids. These results indicate that dLPS can specifically block a variety of endothelial cell responses to LPS and provide support for the hypotheses 1) that dLPS and LPS may interact with a common target molecule on or in endothelial cells, and 2) that dLPS, produced by enzymatic deacylation of LPS in vivo, could inhibit endothelial cell stimulation by LPS and thereby limit the host inflammatory response to invasive gram-negative bacteria.