Approaches to managing bone metastases from breast cancer: the role of bisphosphonates.
Conventional management of metastatic bone disease involves local and systemic therapies in various combinations, along with symptomatic management to provide optimal care. In recent years, it has become clear that adding bisphosphonates to these treatments reduces the incidence and severity of skeletal complications. Bisphosphonates can also relieve metastatic bone pain and improve quality of life, although the extent to which they have demonstrated these effects may differ between agents. While bisphosphonates are the standard of care for the treatment of bone metastases, clinical trials are investigating additional indications for these agents, including the use of intensive dosing regimens for the relief of severe or opioid-resistant metastatic bone pain and adjuvant treatment for the prevention of bone metastases and cancer treatment-induced bone loss. Current and future indications demand effective, well-tolerated and convenient bisphosphonates, and the benefits of different drugs must be balanced against their limitations. The cost-effectiveness of bisphosphonate treatment is also a consideration, given the high economic burden of metastatic bone disease from breast cancer.


Primary mucinous cystadenocarcinoma of the retroperitoneum. Report of a case and literature review.
Primary retroperitoneal mucinous cystadenocarcinoma (PRMC) is a rare tumour, similar to its ovarian counterpart but without any evidence of ovarian, pancreatic or another extra-retroperitoneal origin. Histogenesis of this neoplasm remains uncertain. Mucinous or coelomic metaplasia of retroperitoneal mesothelium has been recently proposed as its origin. In a 43-year-old woman with a 15-cm cystic lesion in the right retroperitoneum mucinous cystadenocarcinoma was diagnosed, and no primary tumour was identified. Two peritoneal endometriotic foci were found on further surgery. We suggest a common histogenesis for PRMC and these endometriotic foci.


Volume overload results in exaggerated cardiac hypertrophy in the atrial natriuretic peptide knockout mouse.
Previous studies suggest that atrial natriuretic peptide (ANP) may act as an autocrine/paracrine factor to modulate cardiac hypertrophy in response to various stimuli. The effect of ANP deficiency on the response to volume overload has not previously been studied. We hypothesised that ANP deficient mice would develop excess cardiac hypertrophy in response to volume overload stress. Male homozygous ANP deficient (Nppa(-/-)) and wildtype (Nppa(+/+)) male mice maintained on either a normal salt (0.55% NaCl) or low salt (0.05% NaCl) diet from weaning were studied after 2 weeks of volume overload from an aorto-caval fistula (ACF). Unoperated littermates served as controls. Left ventricular (LV) structure and function was evaluated by echocardiography. Heart, LV, and lung weights were determined at sacrifice. Myocyte diameter was measured by morphometric analysis of fixed sections of the left ventricle. BP, heart weight, and LV weight were increased in Nppa(-/-) vs. Nppa(+/+) unoperated mice. Nppa(-/-) mice developed exaggerated heart and LV weight compared to Nppa(+/+) mice following ACF. Increased myocyte diameter paralleled increased echo LV wall thickness following ACF in Nppa(+/+) but not Nppa(-/-) mice fed with 0.55% NaCl, indicating that an alternate mechanism contributed to increased wall thickness in Nppa(-/-) mice. Mid-wall shortening was mildly depressed in the Nppa(-/-) vs. Nppa(+/+) genotype following ACF with fed 0.55% NaCl. A 0.05% NaCl diet from weaning normalized BP, but did not prevent exaggerated cardiac enlargement and LV hypertrophy following ACF in Nppa(-/-) mice. ANP-deficient mice exhibited an exaggerated increase in heart and LV weight in response to volume overload, which was not prevented by normalization of blood pressure. The findings suggest that ANP is an important physiologic modulator of the cardiac hypertrophy induced by volume overload.


PPI-Affinity: A Web Tool for the Prediction and Optimization of Protein-Peptide and Protein-Protein Binding Affinity.
Virtual screening of protein-protein and protein-peptide interactions is a challenging task that directly impacts the processes of hit identification and hit-to-lead optimization in drug design projects involving peptide-based pharmaceuticals. Although several screening tools designed to predict the binding affinity of protein-protein complexes have been proposed, methods specifically developed to predict protein-peptide binding affinity are comparatively scarce. Frequently, predictors trained to score the affinity of small molecules are used for peptides indistinctively, despite the larger complexity and heterogeneity of interactions rendered by peptide binders. To address this issue, we introduce PPI-Affinity, a tool that leverages support vector machine (SVM) predictors of binding affinity to screen datasets of protein-protein and protein-peptide complexes, as well as to generate and rank mutants of a given structure. The performance of the SVM models was assessed on four benchmark datasets, which include protein-protein and protein-peptide binding affinity data. In addition, we evaluated our model on a set of mutants of EPI-X4, an endogenous peptide inhibitor of the chemokine receptor CXCR4, and on complexes of the serine proteases HTRA1 and HTRA3 with peptides. PPI-Affinity is freely accessible at https://protdcal.zmb.uni-due.de/PPIAffinity.


Dihydrotestosterone-sensitive neurons in the male rat ventromedial hypothalamus.
Electrical stimulation of the midbrain central gray caused antidromic activation in 273 neurons in and around the hypothalamic ventromedial nucleus in 40 urethan-anesthetized male rats. The latency (range: 2-39 ms) and threshold (100-1,600 microA) of the responses were compared among intact males and orchidectomized males, which received either no treatment, daily injections of testosterone propionate or dihydrotestosterone, or a combined estradiol benzoate and progesterone injection. Recordings were from comparable neuronal pools, because probability distribution for the latency as well as histological localization of each response were not different among groups. Orchidectomy decreased the mean threshold, and either treatment reversed the effect. Dihydrotestosterone increased the mean threshold by reducing the number of cells with thresholds below 600 microA, to a level as in intact males. Estrogen reduced the number of cells responding at 300-900 microA, but at lower thresholds, fell short of replicating the distribution in intact males. Testosterone reinstated the distribution as in intact males. It was concluded that different subgroups of ventromedial hypothalamic neurons with specific sensitivity to metabolites of testosterone project to the central gray.


Factors affecting utilization of dental health services and satisfaction among adolescent females in Riyadh City.
This study was conducted to determine factors affecting utilization of dental health services among intermediate female school students in Riyadh. In addition to assessing their satisfaction with the dental care received during the last dental visit. Self-administered questionnaires were distributed among students attending eight public and four private schools. These schools were selected randomly to represent the four different administrative zones in Riyadh. Of 600 questionnaires distributed, 531 were complete and suitable for analysis. Nearly three quarters of the students visited the dentist more than once during the last 2 years. A bout 75% had their treatment in private dental clinics and 63% made their visits for routine treatment. The quality of dental care was found to be the most encouraging factor for utilization of dental services, whereas, far geographic location of the dental clinics was the most discouraging factor. For those who received treatment in the government clinics, the most discouraging factor was post operative complications (P < 0.0001), while the most encouraging factor was the availability of friendly staff (P < 0.0001). The high cost of dental care was the most discouraging factor for utilizing the dental services for those who visited private clinics (P < 0.0001), while the high quality of dental care was the most encouraging factor (P < 0.009). Students who made their visits because of pain highly considered modern clinics and those recommended by friends as highly encouraging factors (P < 0.002), while they considered the high cost of dental care as discouraging factor for using dental services (P < 0.038). Students who visited the dentist for routine treatment gave the quality of dental care as encouraging for the use of dental clinics (P < 0.0001). Satisfaction with dental care was found to be significantly associated with high quality of dental care, convenient appointment, friendly staff, modern dental clinics and clinics recommended by friends. Quality of dental care, reasonable fees for dental services and close location of dental clinics to students' homes are encouraging factors for utilization of dental services.


Tongue diagnosis index of chronic kidney disease.
To apply non-invasive Automatic Tongue Diagnosis System (ATDS) in analyzing tongue features in patients with chronic kidney disease (CKD). This was a cross-sectional, case-controlled observational study. Patients with CKD who met the inclusion and exclusion criteria were enrolled and divided into the following groups according to renal function and dialysis status: non-dialysis CKD group; end-stage renal disease (ESRD) group; and control group. Tongue images were captured and eight tongue features-shape, color, fur thickness, saliva, fissure, ecchymosis, teeth marks, and red dots-were imaged and analyzed by ATDS. 117 participants (57 men, 60 women) were enrolled in the study, which included 16 in control group, 38 in non-dialysis CKD group, and 63 in ESRD group. We demonstrated significant differences in the fur thickness (p = 0.045), color (p = 0.005), amounts of ecchymosis (p = 0.010), teeth marks (p = 0.016), and red dot (p < 0.001) among three groups. The areas under receiver operating characteristic curve for the amount of ecchymosis was 0.757 ± 0.055 (95% confidence interval, 0.648-0866; p < 0.001). Additionally, with increase in ecchymosis by one point, the risk of CKD dialysis rose by 1.523 times (95% confidence interval, 1.198-1.936; p = 0.001). After hemodialysis, the amount of saliva (p = 0.038), the area of saliva (p = 0.048) and the number of red dots (p = 0.040) were decreased significantly among patients with ESRD. On the contrary, the percentage of coating (p = 0.002) and area of coating (p = 0.026) were increased significantly after hemodialysis. Blood deficiency and stasis with qi deficiency or blood heat syndrome (Zheng pattern) is common in patients with CKD. The risk of CKD dialysis increases with increasing ecchymosis. Hemodialysis can affect saliva, tongue coating, and relieve heat syndrome among ESRD patients.


An assessment of acute biomarker responses in the demersal catfish Cathorops spixii after the Vicuña oil spill in a harbour estuarine area in Southern Brazil.
The Vicuña oil tanker exploded in Paranaguá Bay (South of Brazil), during methanol unloading operations in front of Paranaguá Harbour, on November 15th, 2004, releasing a large amount of bunker oil and methanol. Two weeks after the accident, the acute effects of the Vicuña Oil Spill (VOS) were evaluated in the demersal catfish Cathorops spixii, comparing a contaminated (at the spill site) and a reference site inside the Bay. Data were compared to previous measurements, taken before the accident, in the same species, from the same sites. The physiological biomarkers were the ones that best reflected acute effects of the spill: plasma osmolality, chloride, calcium, magnesium, and potassium. Morphological (liver and gill histopathology) and genetic (piscine micronucleus and DNA strand breaks) biomarkers revealed that damage was already present in fishes from both reference and contaminated sites inside the Bay. Thus, the reference site is not devoid of contamination, as water circulation tends to spread the contaminants released into other areas of the Bay. Acute field surveys of oil spill effects in harbour areas with a long history of contamination should thus be viewed with caution, and whenever possible previous evaluations should be considered for proper appraisal of biomarker sensitivity, especially in mobile bioindicators such as fish.


Ribonucleotide reductase large subunit M1 plays a different role in the invasion and metastasis of papillary thyroid carcinoma and undifferentiated thyroid carcinoma.
Ribonucleotide reductase (RR) has been reported to be associated with several types of cancer while the expression and role of RR in thyroid carcinoma (TC) has not been investigated. Here, we first examined the expression level of three RR subunit proteins (RRM1, RRM2, and RRM2B) in papillary thyroid carcinoma (PTC) and undifferentiated thyroid carcinoma (UTC) patient samples by immunohistochemistry. The results showed that RRM1 was higher expressed in 95.2 % cancer tissues compared with their adjacent normal tissues in 146 PTC samples. The expression level of RRM1 was positively correlated with T stage, lymph node metastasis (LNM), extrathyroidal invasion (ETI), and TNM stage in PTC patients. However, in 12 UTC samples, RRM1 expression was negatively expressed in six cases. To further determine the biological role of RRM1 in TC, ectopic expression or siRNA-mediated knockdown of RRM1 were carried out in the high-differentiated thyroid carcinoma cell line TPC-1 and the poor-differentiated thyroid carcinoma cell line SW579, respectively. In TPC-1 and SW579 cells, overexpression and siRNA knockdown of RRM1 demonstrated that RRM1 promoted DNA synthesis and proliferation in both cell lines as shown by EdU incorporation and cell viability assays. However, RRM1 enhanced cell migration and invasion in TPC-1 cells but inhibited that in SW579 cells as shown by wound healing and transwell assays. Moreover, we also found that RRM1 promoted PTEN expression and reduced Akt phosphorylation in a RR-activity-independent manner in the low-differentiated TC cells but not in the high-differentiated TC cells. In contrast, RRM2 expression was higher expressed in both PTC and UTC patient samples, consisting with its oncogenic role in other cancers. Therefore, we suggest that RRM1 promotes thyroid carcinoma proliferation as a component of RR but may play a different role in the invasion and metastasis of differently differentiated thyroid carcinomas through a non-RR pathway, which could be meaningful to precision treatment of thyroid carcinoma with RR inhibitors.


Identification of a Novel α-herpesvirus Associated with Ulcerative Stomatitis in Donkeys.
An outbreak of ulcerative stomatitis was observed in a donkey (Equus asinus) dairy herd. Similar lesions were also observed on the dams' udders and, sporadically, in genital areas. The lesions typically resolved in 1-3 weeks. An α-herpesvirus, Varicellovirus, genetically related to equid herpesvirus type 3, was identified.


Preoperative Anemia Screening and Treatment Practices in Patients Having Total Joint Replacement Surgery: A Retrospective, Observational Audit.
Surgical patients with preoperative anemia are more likely to experience adverse outcomes. Patient blood management (PBM) guidelines recommend screening and treating patients for anemia preoperatively to enable optimisation before surgery. This study investigates compliance with PBM guidelines and reports the association between length of stay and transfusion risk in patients with preoperative anemia. A retrospective, observational, chart audit that included all patients having primary, total hip and knee replacement surgery between July-December 2018 at a tertiary, metropolitan healthcare facility. Six hundred and seven patients patients were included, 96% (n = 583) patients had blood tests available (full blood count), and 8.1% (n = 49) had iron studies. Most patients 53% (n = 324) were screened between 2 and 6 days before surgery; 14.6% (n = 85) were anaemic preoperatively and only 5.9% (n = 5) of anaemic patients received treatment. Patients who had anemia preoperatively were more likely to receive a blood transfusion (odds ratio 8.65 [95% CI 3.98-18.76]) and stayed longer in hospital (median difference = 1, χ2 LR = 17.2, df=1, p<0.007). Tests ordered for patients having major surgery should include iron studies, renal function, CRP and full blood count to enable detection and classification of preoperative anemia. Timing of screening relative to surgery needs to be sufficient to allow patient optimisation to occur. Appropriate treatment should be provided to anaemic patients to prevent unnecessary blood transfusions and reduce the length of stay. A standardised preoperative anemia pathway may assist in improving practice.


Mortality and causes of death in older patients with schizophrenia.
The aim of this study was to evaluate mortality and causes of death in older patients with schizophrenia in comparison with the general population. The mortality of patients experiencing relapse was also compared with those in remission. The study sample consists of patients (n = 9461) over 65 years by the first of January 1999, with schizophrenia or schizoaffective disorder (ICD-8, ICD-9: 295, ICD-10: F20, F25) as the main register diagnosis during the period 1969-1998. The sample was collected from nationwide registers in Finland and followed up between 1999 and 2008. Overall Standard Mortality Ratio (SMR) of the older schizophrenia patients was 2.69 [95% confidence interval, 2.62-2.76]. For natural causes of death, overall SMR was 2.58 (2.51-2.65; n = 5301), and for unnatural causes of death, it was 11.04 (9.75-12.47; n = 262). The most common causes of death matched those in the general population. Of patients who died during follow-up, 31% (1709/5596) had at least one psychiatric hospitalization within 5 years before follow-up. The SMR for this group was higher (3.92; 3.73-4.11) than in those patients (2.37; 2.29-2.44) with no such treatment during that time. All-cause mortality of older patients with schizophrenia was almost threefold that of general population. They died for similar reasons to the general population; however, deaths for unnatural causes were especially common (accidents and suicides). Those patients still experiencing relapses in older age have an increased risk of death compared with those with schizophrenia in remission.


Intracellular receptors for activated C-kinase in the postmortem human brain: no alteration in Alzheimer disease.
Previous studies have identified a 36-kDa protein that has the properties of an intracellular receptor for the activated C-kinase (RACK1). In the present investigation we quantified levels of RACK1 protein in brains from patients with Alzheimer disease (AD) and age-matched controls. Western analysis using a specific antibody showed that the protein levels for RACK1 were not significantly different in AD brains than in controls, indicating that RACK1 is preserved in AD.


Biomarker S100B in plasma a screening tool for mild traumatic brain injury in an emergency department.
A computerized tomography (CT) scan is an effective test for detecting traumatic intracranial findings after mild traumatic brain injury (mTBI). However, a head CT is costly, and can only be performed in a hospital. To determine if the addition of plasma S100B to clinical guidelines could lead to a more selective scanning strategy without compromising safety. We conducted a single center prospective cohort study at the emergency department. Patients (≥16 years) who received head CT and had a blood draw were included. The primary outcome was the accuracy of plasma S100B to predict the presence of any traumatic intracranial lesion on head CT. We included 495 patients, out of the 74 patients who had traumatic intracranial lesions, 5 patients had a plasma S100B level below the cutoff value of 0.105 ug/L. For the detection of traumatic intracranial injury, S100B had a sensitivity of 0.932 , a specificity of 0.157, a negative predictive value of 0.930, and a positive predictive value of 0.163. Among patients undergoing guideline-based CT scan for mTBI, the use of S100B, would results in a further decrease (14.8%) of CT scans but at a cost of missed injury, without clinical consequence, on CT.


Short-term prediction of HIV infection and AIDS: a critique of the Working Group's Report to the Department of Health.
The Report of the Working Group on the Short-Term Prediction of AIDS/HIV (the Cox Report) is reviewed mainly to assess its calculations of the numbers of people in England and Wales who are infected with the human immunodeficiency virus (HIV). Two main methods are used in the report to estimate this total--the direct method and the back projection method. The direct method estimates the number of people infected with HIV by attempting to specify the numbers of people in various at-risk groups, and the percentage infected in those groups. Of particular significance are the estimates given for male homosexuals. The Cox Report suggests that between 4.0% and 4.7% of the male population aged between 16 and 59 are homosexual, and that between 1.9% and 4.5% of these are HIV antibody-positive. The basis on which these estimates are made is not substantiated by the Report, and it is quite possible that the upper limit given for HIV prevalence in male homosexuals represents an understatement of the actual number by a factor of 2.5 or more. The back projection method estimates HIV prevalence from the numbers of cases of the acquired immunodeficiency syndrome (AIDS) and the incubation function, the relationship between HIV infection and the probabilities of AIDS in each of the years following infection. Using this method the Cox Report fails to produce results that are in accordance with our knowledge of how the epidemic developed during the 1980s. As a consequence of this the various calculations of numbers of HIV antibody-positives to 1987 given in the Cox Report are all almost certainly underestimates.(ABSTRACT TRUNCATED AT 250 WORDS)


Genetic diversity at 15 microsatellite loci among the Adi Pasi population of Adi tribal cluster in Arunachal Pradesh, India.
Genetic polymorphisms at 15 tetrameric short tandem repeat (STR) loci were studied in 203 healthy individuals of Adi Pasi population from Arunachal Pradesh, India. All the loci analyzed were highly polymorphic and there was no significant deviation from the Hardy-Weinberg equilibrium (HWE) excepting D8S1179 and D18S51. Other forensic useful statistical parameters were also calculated and the 15 microsatellite markers selected for this study were found to be suitable for human identification and population genetic studies.


Exploring the properties of Dy2O3-Y2O3 Co-activated telluro-borate glass: Structural, physical, optical, thermal, and mechanical properties.
The successful application of glass-based materials in a wide range of scientific fields depends on the associated physical, optical, thermal, and mechanical properties. This article investigate the structural, Physical, thermal, optical, and mechanical properties of Dy2O3, Y2O3 co-activated telluro-borate glass developed using the melt-quenching method. The glassy quality and the elements component of the specimens were observed using XRD and EDX analyses. The addition of Y2O3 rise the glass density from 2.956 to 3.303 g/cm3 the refractive index from 2.5 to 2.7. These changes are due to the increase in polarizability and non-bridging oxygen (NBO). The photoluminescence (PL) spectra revealed a broad peak at 550 nm and additional weak emission peaks at 573 and 664 nm, respectively. While the observed broader peak can be linked to the convolution of Bi3+ ions transitions corresponding to the non-centrosymmetric site respectively, the weak emission bands are due to 4F9/2 → 6H13/2 and 4F9/2 → 6H11/2 Dy3+ transitions. Hence, the low symmetrical features of both Bi3+ and Dy3+ ions were confirmed. The increase in the Vickers hardness of the glass from 536.7 to 1366.9 indicates the influence of Y2O3 addition on the mechanical properties of the glasses. The findings help to improve our understanding of the behaviour of the glass composition and its prospective applications in disciplines such as photonic, and laser optics.


Enhanced parasympathetic cholinergic activity with galantamine inhibited lipid-induced oxidative stress in obese African Americans.
African Americans (AAs) are disproportionately affected by cardiovascular disease (CVD), they are 20% more likely to die from CVD than whites, chronic exposure to inflammation and oxidative stress contributes to CVD. In previous studies, enhancing parasympathetic cholinergic activity has been shown to decrease inflammation. Considering that AAs have decreased parasympathetic activity compared to whites, we hypothesize that stimulating it with a central acetylcholinesterase (AChE) inhibitor, galantamine, would prevent lipid-induced oxidative stress. To test the hypothesis that acute dose of galantamine, an AChE inhibitor, decreases lipid-induced oxidative stress in obese AAs. Proof-of-concept, double-blind, randomized, placebo-controlled, crossover study that tested the effect of a single dose of 16 mg of galantamine versus placebo on lipid-induced oxidative stress in obese AAs. Subjects were studied on two separate days, one week apart. In each study day, 16 mg or matching placebo was administered before 20% intralipids infusion at doses of 0.8 mL/m2/min with heparin at doses of 200 U/h for 4 h. Outcomes were assessed at baseline, 2 and 4 h during the infusion. Changes in F2-isoprostane (F2-IsoPs), marker of oxidative stress, measured in peripheral blood mononuclear cells (PBMC) and in plasma at baseline, 2, and 4-h post-lipid infusion. Secondary outcomes include changes in inflammatory cytokines (IL-6, TNF alpha). A total of 32 obese AA women were screened and fourteen completed the study (age 37.8 ± 10.70 years old, BMI 38.7 ± 3.40 kg/m2). Compared to placebo, 16 mg of galantamine significantly inhibited the increase in F2-IsoPs in PBMC (0.007 ± 0.008 vs. - 0.002 ± 0.006 ng/sample, P = 0.016), and plasma (0.01 ± 0.02 vs. - 0.003 ± 0.01 ng/mL, P = 0.023). Galantamine also decreased IL-6 (11.4 ± 18.45 vs. 7.7 ± 15.10 pg/mL, P = 0.021) and TNFα levels (18.6 ± 16.33 vs. 12.9 ± 6.16 pg/mL, P = 0.021, 4-h post lipid infusion) compared with placebo. These changes were associated with an increased plasma acetylcholine levels induced by galantamine (50.5 ± 10.49 vs. 43.6 ± 13.38 during placebo pg/uL, P = 0.025). In this pilot, proof-of-concept study, enhancing parasympathetic nervous system (PNS) cholinergic activity with galantamine inhibited lipid-induced oxidative stress and inflammation induced by lipid infusion in obese AAs. ClinicalTrials.gov identifiers NCT02365285.


Outcomes of patients treated with the everolimus-eluting stent versus the zotarolimus eluting stent in a consecutive cohort of patients at a tertiary medical center.
In this study we compared the outcomes of the everolimus-eluting stent (EES) versus the zotarolimus-eluting stent (ZES) in patients treated at a tertiary medical center, with up to one year of follow-up. Unselected consecutive patients were retrospectively recruited following stenting with the ZES (n = 197) or EES (n = 190). The first 100 consecutive patients in each cohort underwent syntax scoring. The primary endpoint of the study was target vessel failure, defined as the combined endpoint of cardiac death, non-fatal myocardial infarction, or target vessel revascularization. Secondary endpoints included target lesion revascularization, target lesion failure, acute stent thrombosis, total death, cardiac death, and non-fatal myocardial infarction. The two groups were similar, including for Syntax scores (19.6 ± 12.8 versus 20.6 ± 13.6), number of stents per patient (2.9 ± 1.9 versus 2.9 ± 2.1), and cardiovascular risk factors. By one year, the primary outcome occurred in 20.8% EES versus 26.7% ZES (P = 0.19) patients. The secondary endpoints were as follows: target lesion revascularization (8.9% versus 20.6%, P = 0.003), target vessel revascularization (18.9% versus 25.6%, P = 0.142), definite and probable stent thrombosis (0% versus 2.5%), non-fatal myocardial infarction (2.7% versus 3.6%), and mortality (3.2% versus 5.1%) for the EES versus the ZES, respectively. EES had similar target vessel failure to ZES, but superior target lesion revascularization and target lesion failure at one year of follow-up in an unselected cohort of patients.


Detection of anticoagulation therapy failures in patients with venous thrombosis.
Results of ultrasonic monitoring of venous patency and fibrinogen uptake testing were evaluated in ten patients with venous thrombosis receiving heparin therapy. Two propagating venous thromboses were detected 24 to 48 hours before massive pulmonary embolism developed, thus emphasizing the usefulness of these methods for detection of anticoagulation therapy failures.


Chemical changes exhibited by latent fingerprints after exposure to vacuum conditions.
The effect of vacuum exposure on latent fingerprint chemistry has been evaluated. Fingerprints were analysed using a quartz crystal microbalance to measure changes in mass, gas chromatography mass spectrometry to measure changes in lipid composition and attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) to determine changes in the content of water, fatty acids and their esters after exposure to vacuum. The results are compared with samples aged under ambient conditions. It was found that fingerprints lose around 26% of their mass when exposed to vacuum conditions, equivalent to around 5 weeks ageing under ambient conditions. Further exposure to vacuum causes a significant reduction in the lipid composition of a fingerprint, in particular with the loss of tetradecanoic and pentadecanoic acid, that was not observed in ambient aged samples. There are therefore implications for sequence in which fingerprint development procedures (for example vacuum metal deposition) are carried out, as well as the use of vacuum based methods such as secondary ion mass spectrometry (SIMS) and matrix-assisted laser desorption ionisation (MALDI) in the study of fingerprint chemistry.


Influence of serum prostate-specific antigen (PSA) level, prostate volume, and PSA density on prostate cancer detection with contrast-enhanced sonography using contrast-tuned imaging technology.
The purpose of this study was to evaluate the influence of the serum prostate-specific antigen (PSA) level, prostate volume, and PSA density on prostate cancer detection with contrast-enhanced sonography using contrast-tuned imaging technology compared with baseline imaging (combination of grayscale and power Doppler imaging). In all, 161 patients were evaluated with grayscale, power Doppler, and contrast-tuned imaging. Biopsy was performed at 10 sites in each patient. When an abnormality was shown on any of these examinations, the biopsy was directed toward the abnormality. Cancer detection between contrast-tuned imaging and baseline imaging was compared for different subgroups according to PSA level (4-10, 10-20, and >20 ng/mL), prostate volume (<35, 35-50, 50-65, and >65 mL), and PSA density (<0.15, 0.15-0.30, 0.30-0.50, and >0.50). In total, 413 sites were malignant in 78 patients. By biopsy site, the accuracy was greater for contrast-tuned imaging than for baseline imaging in all PSA level, prostate volume, and PSA density subgroups except 0.30 to 0.50 (all P < .05). Contrast-tuned imaging had significantly higher sensitivity in the subgroups with PSA levels between 4 and 20 ng/mL, prostate volumes between 35 and 65 mL, and PSA densities between 0.15 and 0.50 than baseline imaging (all P < .05); it also had significantly higher specificity for all PSA level subgroups except 10 to 20 ng/mL, all prostate volume subgroups except 35 to 50 mL, and all PSA density subgroups except 0.30 to 0.50 (all P < .05). Contrast-tuned imaging could improve cancer detection over baseline imaging in patients with different PSA levels, prostate volumes, and PSA densities.


Characterization of Contributing Factors to Variability in Morphine Clearance Through PBPK Modeling Implemented With OCT1 Transporter.
Morphine shows large interindividual variability in its pharmacokinetics; however, the cause of this has not been fully addressed. The variability in morphine disposition is considered to be due to a combination of pharmacogenetic and physiological determinants related to morphine disposition. We previously reported the effect of organic cation transporter (OCT1) genotype on morphine disposition in pediatric patients. To further explore the underlying mechanisms for variability arising from relevant determinants, including OCT1, a physiologically based pharmacokinetic (PBPK) model of morphine was developed. The PBPK model predicted morphine concentration-time profiles well, in both adults and children. Almost all of the observed morphine clearances in pediatric patients fell within a twofold range of median predicted values for each OCT1 genotype in each age group. This PBPK modeling approach quantitatively demonstrates that OCT1 genotype, age-related growth, and changes in blood flow as important contributors to morphine pharmacokinetic (PK) variability.


Activation of Ras in the Vascular Endothelium Induces Brain Vascular Malformations and Hemorrhagic Stroke.
Cerebrovascular malformations (CVMs) affect approximately 3% of the population, risking hemorrhagic stroke, seizures, and neurological deficits. Recently Ras mutations have been identified in a majority of brain arterio-venous malformations. We generated an endothelial-specific, inducible HRASV12 mouse model, which results in dilated, proliferative blood vessels in the brain, blood-brain barrier breakdown, intracerebral hemorrhage, and rapid lethality. Organoid morphogenesis models revealed abnormal cessation of proliferation, abnormalities in expression of tip and stalk genes, and a failure to properly form elongating tubes. These defects were influenced by both hyperactive PI-3' kinase signaling and altered TGF-β signaling. Several phenotypic changes predicted by the in vitro morphogenesis analysis were validated in the mouse model. These data provide a model of brain vascular malformations induced by mutant Ras and reveal insights into intersecting molecular mechanisms in the pathogenesis of brain vascular malformations.


Treatment of a mastoid defect by free anterolateral thigh flap.
Free anterolateral thigh (ALT) flap constitutes an alternative to latissimus dorsi and radial forearm flaps for head and neck reconstruction. The authors report a case of mastoid reconstruction in a patient with multi-operated cholesteatoma associated with tubal dysfunction. This patient presented a fistula of the lateral semicircular canal and invagination of retroauricular soft tissues responsible for non-compensated almost complete areflexia with anacusis. She did not present any signs of cholesteatoma recurrence, but chronic inflammation of the mastoidectomy cavity. The head and neck procedure consisted of translabyrinthine labyrinthectomy: resection of the atrophic retroauricular skin, resection of the vestibular neurosensory tissue and obliteration of the mastoidectomy cavity. An ALT flap measuring 5×5 cm, anastomosed to the superior thyroid artery and facial vein, was used to cover the defect. Careful defatting of the flap allowed filling of the defect, while providing a sufficient quantity of appropriate tissue. The postoperative course was uneventful and the patient was considerably improved. The only donor site sequelae consisted of a thin linear scar. The free anterolateral thigh flap, a reliable, polyvalent flap that can be shaped as needed and which is associated with minimal donor site morbidity, constitutes a good alternative for head and neck reconstruction.


Stab injury to the lumbar spine without neurological involvement in a child.
Stab wound injuries are extraordinary in the child, the thoracic and lumbar spine are the most observed. Patient could be asymptomatic and it could lead to a neurological deficit. We report a case of a 15-year-old boy victim of a stab wound injury with a knife. He was neurologically intact but the local examination showed blood and clear fluid. The patient underwent surgery and the knife was removed with the reparation of a dural tear. Stab wound injuries in child are very rare, the management is clear if there is compression, bleeding or cerebrospinal fluid leakage, and the prognosis depends on the symptoms.


Validating the importance of two acetylcholinesterases in insecticide sensitivities by RNAi in Pardosa pseudoannulata, an important predatory enemy against several insect pests.
The pond wolf spider (Pardosa pseudoannulata) is an important predatory enemy against several insect pests and showed relative different sensitivities to organophosphate and carbamate insecticides compared to insect pests. In our previous studies, two acetylcholinesterases were identified in P. pseudoannulata and played important roles in insecticide sensitivities. In order to understand the contributions of the two acetylcholinesterases to insecticide sensitivities, we firstly employed the RNAi technology in the spider. For a suitable microinjection RNAi method, the injection site, injection volume and interference time were optimized, which then demonstrated that the injection RNAi method was applicable in this spider. With the new RNAi method, it was revealed that both Pp-AChE1 and Pp-AChE2, encoded by genes Ppace1 and Ppace2, were the targets of organophosphate insecticides, but Pp-AChE1 would be more important. In contrast, the carbamate acted selectively on Pp-AChE1. The results showed that Pp-AChE1 was the major catalytic enzyme in P. pseudoannulata and the major target of organophosphate and carbamate insecticides. In a word, an RNAi method was established in the pond wolf spider, which further validated the importance of two acetylcholinesterases in insecticide sensitivities in this spider.


Prophylactic neuroprotective property of Centella asiatica against 3-nitropropionic acid induced oxidative stress and mitochondrial dysfunctions in brain regions of prepubertal mice.
Despite the increasing popularity of Centella asiatica (a well known plant in ayurvedic medicine) globally, evidence demonstrating its protective efficacy against neurotoxicants in animal models is limited. 3-Nitropropionic acid (3-NPA), a fungal toxin is a well known neurotoxicant which induces selective striatal pathology similar to that seen in Huntington's disease. The present study aimed to understand the neuroprotective efficacy of a standardized aqueous extract of C. asiatica (CA) against 3-NPA-induced early oxidative stress and mitochondrial dysfunctions in striatum and other brain regions. We determined the extent of oxidative stress in cytosol and mitochondria of brain regions of male mice (4wk old) given CA prophylaxis (5mg/kgbw) for 10 days followed by 3-NPA administration (i.p., 75mg/kgbw/d) on the last 2 days. The neurotoxicant elicited marked oxidative stress in the untreated mice as evidenced by elevated levels of malondialdehyde, ROS levels and hydroperoxides in the striatum (cytosol and mitochondria), while CA prophylaxis completely attenuated the 3-NPA-induced oxidative stress. 3-NPA also caused significant oxidative stress and protein oxidation in cytosol/mitochondria of other brain regions as well which were predominantly abolished by CA prophylaxis. Significant depletion of GSH levels, total thiols and perturbations in antioxidant enzymic defences in striatum and other brain regions discernible among 3-NPA administered mice were also protected with CA prophylaxis. Interestingly, CA prophylaxis offered varying degree of protection against 3-NPA-induced mitochondrial dysfunctions viz., reduction in the activity of succinic dehydrogenase, ETC enzymes and decreased mitochondrial viability. Collectively these findings clearly suggest that short-term oral intake of a standardized aqueous extract of CA confers marked resistance against the 3-NPA-induced oxidative stress and mitochondrial dysfunctions in brain. Although the precise mechanism/s underlying the prophylactic efficacy of CA merit further investigation, based on these findings, it is hypothesized that it may be wholly or in part related to the enhancement of GSH, thiols and antioxidant machinery in the brain regions of prepubertal mice.


Relationship of loudness-dependent auditory evoked potentials with change-related cortical responses.
Previous studies have suggested that change-related cortical responses are phenomena similar to the onset response and could be applied to the loudness dependence of auditory evoked potential (LDAEP) paradigm. In the present study, we examined the relationship between LDAEP and the change-related response using electroencephalography findings in 50 healthy subjects. There were five conditions (55, 65, 75, 85, and 95 dB) for LDAEP and five similar conditions (abrupt sound pressure increase from 70 to 75, 80, 85, 90, and 95 dB) for the change-related response. Both the onset and abrupt sound pressure increase evoked a triphasic response with peaks at approximately 50 (P50), 100 (N100), and 200 (P200) ms. We calculated the peak-to-peak amplitudes for P50/N100 and N100/P200. Medians and slopes for P50/N100 and N100/P200 amplitudes were calculated and compared between the two measures. Results revealed a significant correlation for both the slope and median for P50/N100 (r = 0.36, 0.37, p = 1.0 × 10-2, 7.9 × 10-3), N100/P200 (r = 0.40, 0.34, p = 4.0 × 10-3, 1.6 × 10-2), and P50/N100/P200 (r = 0.36, 0.35, p = 1.0 × 10-2, 1.3 × 10-2). These results suggested that the change-related response and LDAEP shared generation mechanisms at least partially.


Influence of the sigmaB stress factor and yxaB, the gene for a putative exopolysaccharide synthase under sigmaB Control, on biofilm formation.
Bacillus subtilis forms structured communities of biofilms encased in an exopolysaccharide matrix on solid surfaces and at the air-liquid interface. It is postulated that nonoptimal growth conditions induce this multicellular behavior. We showed that under laboratory conditions a strain deleted for sigB was unable to form a floating pellicle on the surface of a liquid medium. However, overexpression of yxaB, encoding a putative exopolysaccharide synthase, from a p(Spac) promoter in a sigB-deleted strain resulted in partial recovery of the wild-type phenotype, indicating the participation of the YxaB protein in this multicellular process. We present data concerning the regulation of transcription of genes yxaB and yxaA, encoding a putative glycerate kinase. Both genes are cotranscribed as a single transcription unit from a sigma(A)-dependent promoter during vegetative growth of a liquid bacterial culture. The promoter driving transcription of the yxaAB operon is regulated by AbrB. In addition, the second gene in the operon, yxaB, possesses its own promoter, which is recognized by RNA polymerase containing the sigma(B) subunit. This transcription start site is used under general stress conditions, resulting in increased expression.


Long-term outcomes of sacral neuromodulation for lower urinary tract dysfunction: A 23-year experience.
To evaluate the long-term outcomes of sacral neuromodulation (SNM), and patient characteristics that may predict long-term success or complications. A single-center retrospective cohort study was performed of all patients who underwent SNM testing and implantation. Outcome results, resolution of symptoms, and device removal were reported. Multivariable logistic regression was used to identify predictors of success. Cox proportional hazards model was used to identify predictors for device removal. Four hundred and thrity four patients underwent SNM test phase of which 241 (median age 48.0 years, 91.7% [221/241] female) had device implantation and were followed up for median [range] time of 4.0 (3 months-20.5 years) years. Multivariable logistic regression showed that male gender (odds ratio: 0.314; 95% confidence interval: 0.164-0.601, p = .0005) was independently associated with decreased peripheral nerve evaluation success. At final follow-up for patients who originally had device implantation, median (interquartile range) percent of symptoms resolution of all patients was 60.0% (0%-90%) and 69.3% (167/241) had SNM successful outcomes. Cox proportional hazards model showed no difference for time to SNM device removal with respect to patient age, gender, or diagnosis. 69.3% (167/241) patients had at least 1 surgical re-intervention. The most common reason at first surgical re-intervention was lead change only (26.3%, 44/167). SNM is a minimally invasive procedure with good long-term success rates. There is a high revision rate but overall, SNM has a good safety profile and excellent long-term outcomes.


The impact of industrial land mismatch on carbon emissions in resource-based cities under environmental regulatory constraints-evidence from China.
Achieving carbon neutrality has become a global common goal. For China, to reach peak carbon emissions and long-term carbon neutrality, the transformation and development of resource-based cities are essential. This study uses data from 114 prefecture-level resource-based cities from 2008 to 2019 as a sample and empirically tests the impact of industrial land mismatch on carbon emissions using the fixed effects model. In addition, we analyze the heterogeneous influence of environmental regulation as a moderating effect on resource-based cities at different development stages. The study reveals that (1) there is a significant positive correlation between the imbalance in industrial land supply in resource-based cities and carbon emissions. The more severe the imbalance, the higher the carbon emissions. The improper supply mode of industrial land is also positively correlated with carbon emissions, although the impact is not significant. (2) Environmental regulation can significantly curb the carbon emission issues caused by the mismatch and imbalance in the scale of industrial land supply and the improper supply mode of industrial land. (3) Compared to strong resource-based cities, weak resource-security cities have a smaller impact on carbon emissions due to an imbalance in the supply of industrial land. This is mainly because resources in weak resource-security cities are becoming exhausted, making "ecology first, green and low carbon" the main tune for economic and social development. Both types of cities show a positive correlation between the improper supply of industrial land and carbon emissions, although neither is significant. (4) The intensity of the regulatory effect of environmental regulations on resource-based cities is influenced by resource abundance. The suppression of carbon emissions by environmental regulations is more apparent in strong resource-security cities than in weak resource-security cities.


Sustainable and hydrophobic polysaccharide-based mulch film with thermally stable and ultraviolet resistance performance.
This work aimed to construct a polysaccharide-based mulch film with good performance for replacing plastic mulch by coating the glutaraldehyde crosslinking chitosan and humic acid/urea complexes (GCS) into cellulose/humic acid (HA/CE) film. By flow-coating with GCS to construct hierarchical networks, GCS-HA/CE film is endowed with the improved property. The influences of composition with different concentrations on mechanical properties were studied, and the optimum concentration was determined. The tensile strength and elongation of GCS-HA/CE film could reach 53.97 MPa and 12.86 % in dry state, respectively. Results suggest that glutaraldehyde crosslinking reduces moisture content, water solubility, and water vapor permeability, but increases contact angle (94.025°). Meanwhile, the thermostability and ultraviolet resistance were improved. The infrared spectroscopy and X-ray diffractometry demonstrated the successfully crosslinked by glutaraldehyde. Morphological analyses present film has excellent compatibility. In addition, GCS-HA/CE film shows good heat preservation, aging resistance, and biodegradability, indicating certain guiding significance for polysaccharide-based mulch film.


Bile Acid Profiles in Primary Sclerosing Cholangitis and Their Ability to Predict Hepatic Decompensation.
Altered bile acid (BA) homeostasis is an intrinsic facet of cholestatic liver diseases, but clinical usefulness of plasma BA assessment in primary sclerosing cholangitis (PSC) remains understudied. We performed BA profiling in a large retrospective cohort of patients with PSC and matched healthy controls, hypothesizing that plasma BA profiles vary among patients and have clinical utility. Plasma BA profiling was performed in the Clinical Biochemical Genetics Laboratory at Mayo Clinic using a mass spectrometry based assay. Cox proportional hazard (univariate) and gradient boosting machines (multivariable) models were used to evaluate whether BA variables predict 5-year risk of hepatic decompensation (HD; defined as ascites, variceal hemorrhage, or encephalopathy). There were 400 patients with PSC and 302 controls in the derivation cohort (Mayo Clinic) and 108 patients with PSC in the validation cohort (Norwegian PSC Research Center). Patients with PSC had increased BA levels, conjugated fraction, and primary-to-secondary BA ratios relative to controls. Ursodeoxycholic acid (UDCA) increased total plasma BA level while lowering cholic acid and chenodeoxycholic acid concentrations. Patients without inflammatory bowel disease (IBD) had primary-to-secondary BA ratios between those of controls and patients with ulcerative colitis. HD risk was associated with increased concentration and conjugated fraction of many BA, whereas higher G:T conjugation ratios were protective. The machine-learning model, PSC-BA profile score (concordance statistic [C-statistic], 0.95), predicted HD better than individual measures, including alkaline phosphatase, and performed well in validation (C-statistic, 0.86). Patients with PSC demonstrated alterations of plasma BA consistent with known mechanisms of cholestasis, UDCA treatment, and IBD. Notably, BA profiles predicted future HD, establishing the clinical potential of BA profiling, which may be suited for use in clinical trials.


Microalgal cultures for the remediation of wastewaters with different nitrogen to phosphorus ratios: Process modelling using artificial neural networks.
Microalgae have remarkable potential for wastewater bioremediation since they can efficiently uptake nitrogen and phosphorus in a sustainable and environmentally friendly treatment system. However, wastewater composition greatly depends on its source and has a significant seasonal variability. This study aimed to evaluate the impact of different N:P molar ratios on the growth of Chlorella vulgaris and nutrient removal from synthetic wastewater. Furthermore, artificial neural network (ANN) threshold models, optimised by genetic algorithms (GAs), were used to model biomass productivity (BP) and nitrogen/phosphorus removal rates (RRN/RRP). The impact of various inputs culture variables on these parameters was evaluated. Microalgal growth was not nutrient limited since the average biomass productivities and specific growth rates were similar between the experiments. Nutrient removal efficiencies/rates reached 92.0 ± 0.6%/6.15 ± 0.01 mgN L-1 d-1 for nitrogen and 98.2 ± 0.2%/0.92 ± 0.03 mgP L-1 d-1 for phosphorus. Low nitrogen concentration limited phosphorus uptake for low N:P ratios (e.g., 2 and 3, yielding 36 ± 2 mgDW mgP-1 and 39 ± 3 mgDW mgP-1, respectively), while low phosphorus concentration limited nitrogen uptake with high ratios (e.g., 66 and 67, yielding 9.0 ± 0.4 mgDW mgN-1 and 8.8 ± 0.3 mgDW mgN-1, respectively). ANN models showed a high fitting performance, with coefficients of determination of 0.951, 0.800, and 0.793 for BP, RRN, and RRP, respectively. In summary, this study demonstrated that microalgae could successfully grow and adapt to N:P molar ratios between 2 and 67, but the nutrient uptake was impacted by these variations, especially for the lowest and highest N:P molar ratios. Furthermore, GA-ANN models demonstrated to be relevant tools for microalgal growth modelling and control. Their high fitting performance in characterising this biological system can contribute to reducing the experimental effort for culture monitoring (human resources and consumables), thus decreasing the costs of microalgae production.


The role of the ovarian cycle and the effects of mitogen-induced cytokines on human prolactin gene expression in peripheral blood mononuclear cells.
little is known on the influences of normal menstrual cycle on prolactin gene expression in immune cells. to determine the effects of the ovarian cycle on prolactin and its receptor expression. peripheral blood mononuclear cells (PBMC) were obtained from twenty-six normal menstruating women at different intervals of their menstrual cycle. The PBMC were incubated during 24 h in the presence or absence of Concanavalin-A (Con-A) and the gene expression of PRL, PRLR and cytokines was evaluated by qPCR. Prolactin, IL-2 and cAMP were determined in each culture by specific immunoassays. neither PRL nor its receptor expression in PBMC changed significantly among groups, including the cytokines (IL-2, IL-10, and IFNG) studied. Similar results, among groups, were obtained, when PRL expression was stimulated by PGE2 or 8-Br-cAMP. Concanavalin A-stimulated PBMC expressed significantly less prolactin and a significant negative correlation between secreted IL-2 and PRL expression was found. The presence of anti-IL-2 antibodies in Con-A stimulated-cultures significantly increased PRL expression when compared to control cells regardless the hormonal status. these data suggest that the menstrual cycle does not significantly modulate or influence prolactin and cytokines gene expression in PBMC, and indicate that IL-2 may be involved in the Con-A regulation of PRL expression in immune cells.


The concentration of tissue plasminogen activator and urokinase in plasma and tissues of patients with ovarian and uterine tumors.
The concentrations of tissue plasminogen activator (t-PA) and urokinase (UK) were measured in the plasma of patients with benign or malignant ovarian and uterine tumors. Plasma levels of t-PA were higher in patients with malignant ovarian and uterine tumors than in patients with benign tumors. Plasma UK levels were, however, not different between patients with ovarian and uterine tumors (benign or malignant) and normal persons. The concentrations of t-PA and UK of tissues of uterine myoma were lower than those in normal uterine muscular layer. UK levels of tissues of endometrial and cervical cancers were significantly higher than those in normal endometrium and uterine cervix, whereas t-PA levels were not different between these tumors compared with those in normal uterine tissues.


Correction: Mbehang Nguema, P.P., et al. Characterization of ESBL-Producing Enterobacteria from Fruit Bats in an Unprotected Area of Makokou, Gabon. Microorganisms 2020, 8, 138.
The authors wish to make the following corrections to this paper [...].


Schisandrin A ameliorates airway inflammation in model of asthma by attenuating Th2 response.
Asthma is a persistent respiratory ailment that displays periodicity and is linked to the equilibrium of T cells. Several compounds obtained from Chinese herbal medicines display beneficial impacts on T cell regulation and the attenuation of inflammatory mediator synthesis. Schisandrin A, an active lignan derived from the Schisandra fruit, exhibits anti-inflammatory characteristics. In the present study, the network analysis conducted revealed that the nuclear factor-kappaB (NF-κB) signaling pathway is likely a prominent contributor to the anti-asthmatic effects of schisandrin A. In addition, it has been established that the inhibition of cyclooxygenase 2 (COX-2/PTGS2) is likely a significant factor in this process. The results of in vitro experiments have substantiated that schisandrin A can effectively lower the expression of COX-2 and inducible nitric oxide synthase (iNOS) in 16 HBE cells and RAW264.7 cells in a manner that is dependent on the dosage administered. It was able to effectively reduce the activation of the NF-κB signaling pathway while simultaneously improving the injury to the epithelial barrier function. Furthermore, an investigation utilizing immune infiltration as a metric revealed an inequity in Th1/Th2 cells and a surge in Th2 cytokines in asthma patients. In the OVA-induced asthma mice model, it was observed that schisandrin A treatment effectively suppressed inflammatory cell infiltration, reduced the Th2 cell ratio, inhibited mucus secretion, and prevented airway remodeling. To summarize, the administration of schisandrin A has been found to effectively alleviate the symptoms of asthma by impeding the production of inflammation, which includes reducing the Th2 cell ratio and improving the integrity of the epithelial barrier function. These findings offer valuable insights into the potential therapeutic applications of schisandrin A for the treatment of asthma.


Chromosome painting supports lack of homology among sex chromosomes in Oncorhynchus, Salmo, and Salvelinus (Salmonidae).
The sex chromosome pair has been identified previously as the largest submetacentric pair in the genome in several species of the genus Salvelinus (eastern trouts and chars) including S. namaycush (lake trout) and as a large subtelocentric/acrocentric pair in several species of the genus Oncorhynchus (Pacific trouts and salmon). Sex chromosomes have not been identified in Salmo (Atlantic salmon and brown trout). Two paint probes, one specific for the short arm (Yp) and the other for the long arm (Yq) of the sex chromosome pair in Salvelinus namaycush were hybridized to chromosomes of Oncorhynchus mykiss (rainbow trout) and O. tshawytscha (chinook salmon) and Salmo salar (Atlantic salmon) and S. trutta (brown trout). The two probes hybridized to two different autosomal pairs in each of the Oncorhynchus species, supporting lack of homology between the sex chromosomes in the two genera. The Yp probe hybridized to interstitial regions on two different chromosome pairs in S. salar and one pair in S. trutta. The Yq probe hybridized to a different pair in both species.


Proposed Sheffield quantitative criteria in cervical cytology to assist the diagnosis and grading of squamous intra-epithelial lesions, as some Bethesda system definitions require amendment.
This study assesses the accuracy of published quantitative and qualitative criteria in the Bethesda System (TBS) for squamous intra-epithelial lesions. Quantitative image analysis was undertaken on illustrations from TBS publications and also from slides in Cytology Training Centre teaching sets. Comparisons were also made with the British Society for Clinical Cytology (BSCC) terminology in cervical cytology, using the illustrations in their terminology publication and amalgamating the results into their proposed new two-tier model. TBS quantitatively defines low-grade squamous intra-epithelial lesions (LSIL) in both conventional and liquid-based cytology (LBC) preparations as showing nuclear enlargement more than x3 the area of a normal intermediate squamous cell nucleus. This study found that the increase in mean nuclear area was limited to only x2 in conventional preparations. In LBC (SurePath preparations, there was only a statistically non-significant x1.2 increase. This study identified a progressive and statistically significant reduction in mean cytoplasmic area from normal intermediate cells to LSIL and then to high-grade squamous intra-epithelial lesions (HSIL) in both conventional and LBC preparations. Furthermore, the most consistent quantitative finding in both conventional and LBC preparations was a statistically significant increase in the mean area and diameter ratios from normal intermediate cells to LSIL and then to HSIL. In all instances this varied from x2 to just below x3. This is in agreement with TBS, which states that the cytoplasmic area in HSIL is decreased leading to a marked increase in nuclear to cytoplasmic (NC) ratio. With the exception of an increase in mean nuclear area in conventional preparations from normal intermediate cells to LSIL, the predominant cause for this increase in NC ratios was a reduction in mean cytoplasmic area. The numerical increase in NC ratio for LSIL identified in this study was greater than implied by the 'slightly increased' statement in TBS. TBS comments that some HSIL cells can have the same degree of nuclear enlargement as in LSIL and that other HSIL cells may have much smaller nuclei than in LSIL. Both of these qualitative comments were supported in this study. The mean diameter NC ratios of 33% and 50% could provide useful diagnostic assistance in the distinction of normal intermediate cells and LSIL and between LSIL and HSIL, respectively. Because of overlapping individual ranges, however, additional diagnostic features such as nuclear morphology must be used in the distinction of normal intermediate cells, LSIL and HSIL. No statistical difference was identified in the mean diameter NC ratios between ASC-US and LSIL in TBS publications. In addition, the proposed new BSCC low and high grades of squamous abnormality were not statistically different from ASC-US/LSIL and HSIL, respectively. This provides support that the proposed BSCC two-tier system of squamous abnormalities is comparable to TBS. This study shows that LBC has variable but major and significant effects on nuclear and cytoplasmic morphology and that quantitative definitions in conventional preparations cannot be automatically extrapolated to LBC methodology. The study shows that some TBS quantitative and qualitative criteria require amendment and that an alternative quantitative approach, such as diameter NC ratio has a more valid scientific evidence base. Furthermore, use of NC ratios avoids the problems associated with the variable changes in nuclear and cytoplasmic areas, occurring between conventional and different commercial LBC preparations. By contrast, classifications based on area comparisons must be tailored to the specific conventional or commercial LBC preparation.


Effluent N-terminal expressed in renal cell carcinoma/mesothelin predicts increased peritoneal permeability in patients undergoing peritoneal dialysis.
We investigated whether N-terminal and C-terminal products of expressed in renal cell carcinoma/mesothelin (N-ERC and C-ERC) in peritoneal effluent can predict peritoneal permeability in patients undergoing peritoneal dialysis (PD). Thirty-seven peritoneal effluent samples were obtained from 26 PD patients. High transport status was determined by the peritoneal equilibration test as a dialysate/plasma ratio of creatinine (D/P Cr) ≥ 0.81. Effluent cancer antigen 125 (CA125) was used as a reference. Effluent N-ERC concentration was better correlated with D/P Cr than effluent C-ERC or CA125 concentration. In multivariate analyses, effluent N-ERC and C-ERC, but not CA125, were significant predictors of high transport status after adjusting for age, PD duration, and residual renal Kt/V. ROC analysis showed that effluent N-ERC was the best predictor of high transport status among those three biomarkers. Effluent N-ERC predicts increased peritoneal permeability in patients undergoing PD.


Knowledge regarding breast cancer among Congolese women in Kinshasa, Democratic Republic of the Congo.
Breast cancer is the most frequent type of cancer in women and is characterized by late clinical signs in developing countries, including the Democratic Republic of the Congo. One of the main reasons of death from breast cancer is lack of awareness and screening, which has led to late diagnosis (at an advanced stage). This study aims to measure women's knowledge regarding breast cancer in Kinshasa, in the Democratic Republic of the Congo. A cross-sectional study of 489 women aged 20-65 years was conducted. Data was collected using a predesigned, tested, self-administered questionnaire. The questionnaire included specific sections to test the participants' knowledge related to breast cancer and its screening, and practices related to breast self-examination (BSE). Bivariate and multivariate analyzes were used. Our results indicated that 22.09% of the participants had good breast cancer knowledge and 77.91% had poor breast cancer knowledge. Overall, 322 (65.85%) participants recognized that BSE is a valuable method for early screening of BSE. In total, 136 (27.81%) respondents had learned to do the BSE and 216 (44.17%) had reported doing it. Two hundred and ninety-two (59.71%) respondents mentioned that any woman was at risk for breast cancer and 357 (71.78%) mentioned that it was possible to prevent breast cancer. Determinants of an adequate level of knowledge were higher/university educational level (adjusted odds ratio = 2.70; 95% confidence interval: 1.27-5.73; p = .010) and having previously been screened for breast cancer (adjusted odds ratio = 2.31; 95% confidence interval: 1.40-3.83; p = .001). The majority (77.91%) of women have demonstrated poor knowledge of signs/symptoms, risk factors, and screening methods of breast cancer. Additional efforts should be made through women's healthcare workers to raise knowledge of breast cancer screening.


Thyroid-hormone modulation of the number of beta-adrenergic receptors in rat fat-cell membranes.
Adipocytes from thyroidectomized rats contain 3 times less [3H]dihydroalprenolol-binding sites (beta-adrenergic receptors) than adipocytes from euthyroid animals. This alteration is not solely due to cell-size differences, but also to a thyroidectomy-induced defect in beta-adrenergic receptor density per adipocyte surface area, a defect that is furthermore corrected by tri-iodothyronine treatment.


Implementation of the frailty assessment to improve liver transplant outcomes.
The majority of patients undergoing Orthotopic Liver Transplantation (OLT) have increased in age, therefore chronological age may have become an unreliable parameter for supporting clinical decisions. The age-related deficit accumulation model measuring frailty proposed by Rockwood et al., may propose an alternative in providing an estimate of an individual's biological age. No Frailty Index (FI) tailored specifically for OLT patients exists to date. Forty-three consecutive OLT patients with ≥ 20 years of survival with a functioning graft were included in our study. The FI was computed taking to account 39 items (FI-39), meeting the standard criteria for internal validation. Endpoints were polypharmacy, and recent Emergency Room admission. The mean age of our population was 69 (sd 9) years. The mean FI-39 was 0.23 (sd 0.1). The FI-39 was associated with polypharmacy [odds ratio (OR) 1.13; Confidence interval (95%CI) 1.03-1.24; p = 0.01], and recent Emergency Room admission [beta coefficient + 1.98; 95%CI + 0.26, + 3.70; p = 0.03], independent for age and sex. This study demonstrates that an FI can be derived from data collected during routine clinical follow-up and allows for improved differentiation related to the OLT clinical complexity in OLT patients, independent of chronological age. This may lead to the adoption of FI-39 to improve personalized OLT patient care.


Metabotropic glutamate 1 receptor distribution and occupancy in the rat brain: a quantitative autoradiographic study using [3H]R214127.
We used the selective metabotropic glutamate (mGlu) 1 receptor antagonist [3H]1-(3,4-dihydro-2H-pyrano[2,3-b]quinolin-7-yl)-2-phenyl-1-ethanone ([3H]R214127) to investigate the distribution of mGlu1 receptor binding sites in rat brain. We found high mGlu1 receptor binding in the cerebellum, thalamus, dentate gyrus and medial central gray, moderate binding within the CA3 of the hippocampus and hypothalamus, and low mGlu1 receptor binding in the basal ganglia and cortex. The mGlu1 receptor is also present in variable degree in the dorsal lateral septal nucleus, amygdala, interpeduncular nucleus and median raphe nucleus. Additionally, we employed [3H]R214127 autoradiography as a means of investigating the occupancy of central mGlu1 receptors following in vivo administration of mGlu1 receptor antagonists that prevent binding of this radioligand. We found that the mGlu1 receptor antagonist (3aS,6aS)-6a-naphtalan-2-ylmethyl-5-methyliden-hexahydro-cyclopenta[c]furan-1-on (BAY 36-7620), administered subcutaneously (s.c.) at 10 mg/kg, only occupied about 30% of cerebellar and thalamic mGlu1 receptors. The mGlu1/5 receptor antagonist 2-quinoxaline-carboxamide-N-adamantan-1-yl (NPS 2390) exhibited a relatively high potency in occupying mGlu1 receptors in rat cerebellum (ED50 = 0.75 mg/kg, s.c.) and thalamus (ED50 = 0.63 mg/kg, s.c). In the future, this method can be employed to gain more insight into the in vivo profile and central activity of potential therapeutic agents that act upon the mGlu1 receptor.


The Hidden Ethics Curriculum in Two Canadian Psychiatry Residency Programs: A Qualitative Study.
The authors describe the hidden ethics curriculum in two postgraduate psychiatry programs. Researchers investigated the formal, informal, and hidden ethics curricula at two demographically different postgraduate psychiatry programs in Canada. Using a case study design, they compared three sources: individual interviews with residents and with faculty and a semi-structured review of program documents. They identified the formal, informal, and hidden curricula at each program for six ethics topics and grouped the topics under two thematic areas. They tested the applicability of the themes against the specific examples under each topic. Results pertaining to one of the themes and its three topics are reported here. Divergences occurred between the curricula for each topic. The nature of these divergences differed according to local program characteristics. Yet, in both programs, choices for action in ethically challenging situations were mediated by a minimum standard of ethics that led individuals to avoid trouble even if this meant their behavior fell short of the accepted ideal. Effective ethics education in postgraduate psychiatry training will require addressing the hidden curriculum. In addition to profession-wide efforts to articulate high-level values, program-specific action on locally relevant issues constitutes a necessary mechanism for handling the impact of the hidden curriculum.


Cytokine pathway variants modulate platelet production: IFNA16 is a thrombocytosis susceptibility locus in humans.
Inflammatory stimuli have divergent effects on peripheral platelet counts, although the mechanisms of thrombocytopenic and thrombocytotic responses remain poorly understood. A candidate gene approach targeting 326 polymorphic genes enriched in thrombopoietic and cytokine signaling pathways was applied to identify single nucleotide variants (SNVs) implicated in enhanced platelet responses in cohorts with reactive thrombocytosis (RT) or essential (myeloproliferative neoplasm [MPN]) thrombocytosis (ET). Cytokine profiles incorporating a 15-member subset, pathway topology, and functional interactive networks were distinct between ET and RT, consistent with distinct regulatory pathways of exaggerated thrombopoiesis. Genetic studies using aggregate (ET + RT) or ET-restricted cohorts identified associations with 2 IFNA16 (interferon-α16) SNVs, and the ET associations were validated in a second independent cohort (P = .0002). Odds ratio of the combined ET cohort (n = 105) was 4.92, restricted to the JAK2V617F-negative subset (odds ratio, 5.01). ET substratification analysis by variant IFNA16 exhibited a statistically significant increase in IFN-α16 levels (P = .002) among 16 quantifiable cytokines. Recombinantly expressed variant IFN-α16 encompassing 3 linked non-synonymous SNVs (E65H95P133) retained comparable antiviral and pSTAT signaling profiles as native IFN-α16 (V65D95A133) or IFN-α2, although both native and variant IFN-α16 showed stage-restricted differences (compared with IFN-α2) of IFN-regulated genes in CD34+-stimulated megakaryocytes. These data implicate IFNA16 (IFN-α16 gene product) as a putative susceptibility locus (driver) within the broader disrupted cytokine network evident in MPNs, and they provide a framework for dissecting functional interactive networks regulating stress or MPN thrombopoiesis.


Multidisciplinary international survey of post-operative radiation therapy practices after nipple-sparing or skin-sparing mastectomy.
Skin sparing mastectomy (SSM) and nipple-sparing mastectomy (NSM) have entered routine surgical practice for breast cancer, though their oncologic safety has not been established in randomized controlled trials. The aim of this study was to evaluate and compare radiation oncologists' and breast surgeons' opinions concerning the indications of post-operative radiation therapy (PORT) after SSM and NSM. Radiation oncologists and breast surgeons from North America, South America and Europe were invited to contribute in this study. A 22-question survey was used to evaluate their opinions. A total of 550 physicians (298 radiation oncologists and 252 breast surgeons) answered the survey. The majority of responders affirmed that PORT should be performed in early-stage (stages I and II) breast cancer for patients who present with risk factors for relapse after SSM and NSM. They considered age, lymph node involvement, tumor size, extracapsular extension, involved surgical margins, lymphovascular invasion, triple negative receptor status and multicentric presentation as major risk factors. Considering that after SSM and NSM, residual breast tissue can be left behind, the residual tissue considered as acceptable in the context of an oncologic surgery were 1-5 mm for breast surgeons. There is no consensus for the necessity of evaluating residual breast tissue through breast imaging. Although the indications of PORT after SSM and NSM vary among practitioners, standard risk factors for relapse are considered as important by radiation oncologists and breast surgeons.


Low glutathione levels in brain regions of aged rats.
Glutathione (GSH) was measured in 6 regions of brain and liver of young adult, middle-aged and aged rats. GSH levels were significantly lower in cortex, cerebellum, striatum, thalamus and hippocampus of aged rats, while no changes were observed in liver as compared to young adult rats. On the other hand, lipid peroxidation as measured by thiobarbituric acid-reactive products increased significantly in all the regions of brain examined and in the liver of aged rats. Since GSH plays an important role as a cellular protectant against oxygen radical-mediated injury, decreased levels of GSH in aged rat brain are indicative of the vulnerability of the aged cerebral tissue to oxidative injury.


Gating of skeletal and cardiac muscle sodium channels in mammalian cells.
1. Sodium channel ionic current (INa) and gating current (Ig) were compared for rat skeletal (rSkM1) and human heart Na+ channels (hH1a) heterologously expressed in cultured mammalian cells at approximately 13 C before and after modification by site-3 toxins (Anthopleurin A and Anthopleurin B). 2. For hH1a Na+ channels there was a concordance between the half-points (V ) of the peak conductance-voltage (G-V) relationship and the gating charge-voltage (Q-V) relationship with no significant difference in half-points. In contrast, the half-point of the Q-V relationship for rSkM1 Na+ channels was shifted to more negative potentials compared with its G-V relationship with a significant difference in the half-points of -8 mV. 3. Site-3 toxins slowed the decay of INa in response to step depolarizations for both rSkM1 and hH1a Na+ channels. The half-point of the G-V relationship in rSkM1 Na+ channels was shifted by -8.0 mV while toxin modification of hH1a Na+ channels produced a smaller hyperpolarizing shift of the V by -3.7 mV. 4. Site-3 toxins reduced maximal gating charge (Qmax ) by 33% in rSkM1 and by 31% in hH1a, but produced only minor changes in the half-points and slope factors of their Q-V relationships. In contrast to measurements in control solutions, after modification by site-3 toxin the half-points of the G-V and the Q-V relationships for rSkM1 Na+ channels demonstrated a concordance similar to that for hH1a. 5. Qmax vs. Gmax for rSkM1 and hH1a Na+ channels exhibited linear relationships with almost identical slopes, as would be expected if the number of electronic charges (e-) per channel was comparable. 6. We conclude that the faster kinetics in rSkM1 channels compared with hH1a channels may arise from inherently faster rate transitions in skeletal muscle Na+ channels, and not from major differences in the voltage dependence of the channel transitions.


Effects of two kinds of noradrenergic ADHD medicines on sign-tracking and goal-tracking in male rats.
Sign- and goal-tracking are behaviors seen in many species when a conditioned stimulus and it's corresponding unconditioned stimulus are presented at separate locations, and have been the focus of studies on appetitive conditioned and drug dependence. The neurochemical basis of sign-tracking is of interest for both studies of basic conditioning and addiction. In this work, I examined the role of norepinephrine by employing two noradrenergic drugs used for attention-deficit hyperactivity disorder (ADHD)-(a) atomoxetine, a norepinephrine reuptake blocker, and (b) guanfacine, an α2A-adrenergic receptor agonist. Sprague-Dawley rats were trained using a standard Pavlovian conditioning procedure with a retractable lever as conditioned stimulus and sucrose pellets as unconditioned stimulus. It was found that while atomoxetine reduced both sign- (both doses) and goal-tracking (only at the higher dose), guanfacine did not have any effect on either behavior. While norepinephrine reuptake blocking may be an effective strategy for reducing sign-tracking, manipulation of the α2A-adrenergic receptor appears less viable. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Role of pine needle biochar in operation and stability of anaerobic processes.
Utility of biochar addition in anaerobic processes for promoting direct interspecies electron transfer (DIET) is demonstrated in this research. Biochar produced from pyrolysis of pine needle forest residue was used as conductive material for DIET. Three CSTRs were operated in parallel with and without biochar addition in fed-batch mode. Reactor without biochar which represented indirect interspecies electron transfer (IIET) exhibited wide variation in pH and VFA and took longer period during startup. All the rectors were operated at steady state with an OLR ranging from 0.5 to 1.75 kg-COD/m3.d. As OLR increased, performance of reactor without biochar resulted in rapid pH drop and increase in VFA, leading to its eventual failure at OLR of 1.75 kg-COD/m3.d. As against to this, performance of reactors with biochar remained robust and relatively unaffected at higher OLR values. Daily VFA accumulation from fed-batch mode always remained highest in reactor without biochar.


Aging with HIV: an overview of an urban cohort in Rio de Janeiro (Brazil) across decades of life.
The introduction of highly active antiretroviral therapy during the 1990s was crucial to the decline in the rates of morbidity and death related to the acquired immunodeficiency syndrome (AIDS) and turned human immunodeficiency virus (HIV) infection into a chronic condition. Consequently, the HIV/AIDS population is becoming older. The aim of this study was to describe the immunological, clinical and comorbidity profile of an urban cohort of patients with HIV/AIDS followed up at Instituto de Pesquisa Clinica Evandro Chagas, Oswaldo Cruz Foundation in Rio de Janeiro, Brazil. Retrospective data from 2307 patients during January 1st, 2008 and December 31st, 2008 were collected. For continuous variables, Cuzick's non-parametric test was used. For categorical variables, the Cochran-Armitage non-parametric test for tendency was used. For all tests, the threshold for statistical significance was set at 5%. In 2008, 1023 (44.3%), 823 (35.7%), 352 (15.3%) and 109 (4.7%) were aged 18-39, 40-49, 50-59 and ≥60 years-old, respectively. Older and elderly patients (≥40 years) were more likely to have viral suppression than younger patients (18-39 years) (p<0.001). No significant difference in the latest CD4(+) T lymphocyte count in the different age strata was observed, although elderly patients (≥ 50 years) had lower CD4(+) T lymphocyte nadir (p<0.02). The number of comorbidities increased with age and the same pattern was observed for the majority of the comorbidities, including diabetes mellitus, dyslipidemia, hypertension, cardiovascular diseases, erectile dysfunction, HCV, renal dysfunction and also for non-AIDS-related cancers (p<0.001). With the survival increase associated to successful antiretroviral therapy and with the increasing new infections among elderly group, the burden associated to the diagnosis and treatment of the non-AIDS related HIV comorbidities will grow. Longitudinal studies on the impact of aging on the HIV/AIDS population are still necessary, especially in resource-limited countries.


Induction of metallothionein in liver and changes of essential metal levels in selected tissues by three dextran derivatives.
Three dextran derivatives (dextran sulfate, DEAE-dextran and Dextran T500) were injected intraperitoneally into mice to study the induction of zinc-thionein in the liver, and the changes of essential metal levels in the liver, kidneys and spleen. The former was investigated with a high performance liquid chromatograph equipped with an atomic absorption spectrophotometer, and the latter with an inductively coupled plasma-atomic emission spectrometer. Dextran sulfate and DEAE-dextran induced a large amount of hepatic zinc-thionein dose-dependently, while Dextran T500 did not induce metallothionein substantially at the doses studied 20, 40 and 60 mg/kg body wt). The injection of dextran sulfate resulted in a significant increase of spleen weight, with a transitory increase of calcium concentration in the three tissues and a significant decrease of iron level in the spleen. In accord with the induction of zinc-thionein by dextran sulfate and DEAE-dextran, zinc concentration in the liver also increased transitionally after both injections and the time-course of the hepatic zinc level in dextran sulfate showed a close resemblance to that of the calcium one.


Cell biology and clinical implications of adhesion molecules in colorectal diseases: colorectal cancers, infections and inflammatory bowel diseases.
Adhesion molecules are transmembrane proteins that can anchor cytoskeletal proteins on the cytoplasmic side of the cell membrane, while also connecting extracellular structures on the outer surface of the cell membrane. In addition to physical linkages between the extracellular environment and the cytoskeleton, adhesive complexes participate in important signal transduction systems as modulators or receptors. Their functions in cell signaling are probably at least as important as their cytoskeletal and cell attachment properties. Understanding these regulatory functions appears to be of importance in determining of pathological characteristic of numerous diseases. Expression and functional activity of various adhesion molecules have been found in different diseases affecting the colorectum. In this review we summarize recent advantages about the cell biology these diseases and clinical implications.


Relationships between serum leptin and bone markers during stable weight, weight reduction and weight regain in male and female judoists.
Despite a preliminary understanding of leptin-skeletal interactions, data in humans are inconsistent and the exact roles of leptin on bone metabolism have not yet been defined. The aim of this study was to examine the possible role of leptin in the regulation of bone metabolism in healthy, physically trained adults. Body composition and bone mass (dual-energy X-ray absorptiometry), anthropometry, serum leptin, insulin, cortisol, osteocalcin, C-terminal telopeptide of type I collagen (CTx) and total plasma proteins were measured in judoists at normal body weight, after weight reduction and after weight regain. Physical training, weight cycling history, menstrual status and nutritional intake using a 7-day food record were assessed. Precompetitive weight loss averaged 4 +/- 0.3% of bodyweight and resulted in a significant decrease in leptin levels of 64% (P < 0.001) and of 31% for insulin (P < 0.0001). CTx and cortisol concentrations rose by 33% (P < 0.0001) and 81% (P < 0.05) respectively. Osteocalcin and total plasma protein remained unaffected by weight loss. A 4 +/- 0.5% weight regain induced a 276% increase in leptin levels (P < 0.001) and an 18% increase in insulin (P < 0.001). CTx and cortisol decreased by 23% (P < 0.0001) and 27% (P < 0.05) respectively. Changes in leptin were significantly correlated with changes in bone resorption marker in response to both weight loss (r = 0.56, P < 0.01) and regain (r = 0.44, P < 0.05). These findings suggest that leptin is involved in the regulation of bone metabolism in healthy adults and might play a potential role in the prevention of osteoporosis.


Potentially Toxic Metal Accumulation in Spinach (Spinacia oleracea L.) Irrigated with Industrial Wastewater and Health Risk Assessment from Consumption.
This study aimed to determine the potentially toxic metal contents in soil and spinach samples in areas irrigated with industrial wastewater and to evaluate the potentially toxic metal accumulation in spinach samples according to pollution indices. Water, soil and spinach samples were analysed using atomic absorption spectrophotometer (Perkin-Elmer AAS-300). In this study, it was determined that the potentially toxic metal values in the spinach samples irrigated with groundwater and sugar industry wastewater varied between 1.59 and 1.84, 0.22-0.68, 0.56-1.14, 1.41-1.56, 1.62-3.23, 0.57-1.02, 0.86-1.33, 0.20-0.32 and 0.35-2.10 mg/kg for Cd, Co, Cr, Cu, Fe, Ni, Pb, Zn and Mn, respectively. It was concluded that the difference between the metal values in the spinach samples according to the irrigation sources was statistically significant, except for Cu and Pb (p > 0.05). According to the results of this study, there is no health risk for Pb, Co and Cr with HRI values below 1.0, while there is a risk for Cd, Cu, Fe, Ni, Mn and Zn. The much higher HRI values of Cd than 1 (196.8 and 169.6) suggested that this metal is likely to cause significant health problems in the region.


'Fit for purpose' health impact assessment: a realistic way forward.
The UK government is committed to health impact assessment (HIA) as a means of ensuring that health will be a key consideration in policy formulation and other public decision making. However there has been some debate about whether current HIA practice can reliably inform decision making. In particular consultation with stakeholders and literature reviewing, key tools used in HIA, are said to suffer from a number of conceptual and methodological problems, which can undermine the validity of the assessment. In this paper, we argue that the philosophical nature of HIA, its purpose and its contribution to the promotion of public health is still being established. We outline our own HIA practice, which is based on a broad philosophy of 'fit for purpose' i.e. what is this HIA for and what is its spatial, temporal, social and political context. We suggest that it is important to guard against unrealistic expectations and illusions of total objectivity and precision in the HIA process. HIA 'screening' is capable of delivering benefits by making policies, programmes and projects, more health conscious. Once we move beyond this basic expectation and wish to be able to make judgements about the relative health benefits of alternative courses of action, the potential resource intensiveness of the process increases considerably. Even at a high level of resource usage any conclusions reached through the HIA process will always be, in part, subjective and therefore likely to be contested. We must decide what we want, what we are prepared to legislate for and what we are prepared to pay for in the HIA process.


Surgical treatment for aneurysm of aberrant subclavian artery based on a case report and a review of the literature.
Experiences with the recent successful treatment of a patient with an aneurysm arising from an aberrant subclavian artery are described. The reported experiences with surgical treatment by others were reviewed in detail: Only 16 such patients were found, with a surprising frequency of serious complications. These data led to the conclusion that a two-stage approach, through right cervical and left thoracotomy incisions, seems to offer the ideal method of treatment for this unusual problem.


Thromboxane prostanoid signaling in macrophages attenuates lymphedema and facilitates lymphangiogenesis in mice : TP signaling and lymphangiogenesis.
Accumulating evidence suggests that prostaglandin E2, an arachidonic acid (AA) metabolite, enhances lymphangiogenesis in response to inflammation. However, thromboxane A2 (TXA2), another AA metabolite, is not well known. Thus, this study aimed to determine the role of thromboxane prostanoid (TP) signaling in lymphangiogenesis in secondary lymphedema. Lymphedema was induced by the ablation of lymphatic vessels in mouse tails. Compared with wild-type mice, tail lymphedema in Tp-deficient mice was enhanced, which was associated with suppressed lymphangiogenesis as indicated by decreased lymphatic vessel area and pro-lymphangiogenesis-stimulating factors. Numerous macrophages were found in the tail tissues of Tp-deficient mice. Furthermore, the deletion of TP in macrophages increased tail edema and decreased lymphangiogenesis and pro-lymphangiogenic cytokines, which was accompanied by increased numbers of macrophages and gene expression related to a pro-inflammatory macrophage phenotype in tail tissues. In vivo microscopic studies revealed fluorescent dye leakage in the lymphatic vessels in the wounded tissues. The results suggest that TP signaling in macrophages promotes lymphangiogenesis and prevents tail lymphedema. TP signaling may be a therapeutic target for improving lymphedema-related symptoms by enhancing lymphangiogenesis.


Alternatives to standard unfractionated heparin for pediatric hemodialysis treatments.
Despite advances in biomaterials and dialyzer design, thrombin generation occurs in the dialysis circuit because of platelet and leukocyte activation. As such, anticoagulation is required by the majority of children for successful dialysis to prevent clotting in the venous air detector and the capillary dialyzer, particularly for small children with slower blood flow rates. For many years unfractionated heparin has been the standard anticoagulant of choice, but is now being challenged by low-molecular-weight heparins (LMWHs) because they are simple to administer and reliable, particularly as the cost differential has been eroded. Alternative, nonheparin anticoagulants are more frequently available, but are often restricted to special circumstances: patients at high risk of hemorrhage; heparin allergy; or heparin-induced thrombocytopenia. These nonheparin alternatives are significantly more expensive than heparins, and may add a degree of complexity, such as citrate, which is a regional anticoagulant, although citrate-containing dialysate may permit short anticoagulant-free dialysis sessions. Systemic anticoagulants required for immune-mediated, heparin-induced thrombocytopenia are expensive and either have short half-lives, and therefore require continuous infusions, or prolonged half-lives, which, although allowing simple bolus administration, increases the risk of drug accumulation, over-dosage and hemorrhage.


[Aerosoltherapy and operative aspects in cystic fibrotic children with sinusitis maxillaris (author's transl)].
Cystic fibrosis is often associated with chronic sinusitis maxillaris. Endonasal fenetration recommended improves aerosol efficiency on the mucosa and simultaneous improves swab and rinsing treatment.


Reward magnitude, but not time of day, influences the trial-spacing effect in autoshaping with rats.
The arousal hypothesis of the trial-spacing effect suggests that spaced-trial training increases emotional arousal and thus invigorates Pavlovian behavior, relative to massed-trial conditions. Emotional arousal was manipulated by varying reinforcer magnitude during training (either one or five food pellets/trial, across groups). In addition, autoshaping training was administered either in the morning (0900 h) or in the evening (1700 h). Rats were housed in an enclosed colony room and exposed to a regular light:dark cycle (light from 0700 to 1900 h). Available evidence indicates that reinforcer magnitude and time of day are related to arousal levels. As expected, a larger reinforcer magnitude led to a highly significant trial spacing effect. Evening training led to a higher response rate than morning training, but the trial-spacing effect was equally strong whether training was administered in the morning or in the evening. These results provide partial support for the arousal hypothesis and are discussed in the context of research on schedule-induced behavior.


Accuracy associated with the activity determination by in situ gamma spectrometry of naturally occurring radionuclides in soils.
In situ gamma spectrometry (ISGS) is a technique mainly focused on the determination of man-made radionuclides deposited on soils. It is widely used for the radioactive characterization of soils in which there has been an incorporation of such radionuclides, especially 137Cs. Its use for the activity determination of naturally occurring radionuclides in soils has been more limited, and the accuracy associated with those measurements has yet to be treated extensively. There are numerous factors affecting the accuracy of the activity determination of naturally occurring radionuclides, such as the assumed soil geometry, the soil's geological and mineral composition, its moisture content, etc. The present work studies the accuracy associated with the ISGS determination of the activity concentrations of natural radionuclides in soils using a portable HPGe detector. For 40K and 232Th activity determinations, the uncertainties associated with ISGS are generally of the order of 15%. However, 226Ra activity determined from its daughters 214Pb and 214Bi can be significantly overestimated when there is a major presence of 222Rn in the air around the detector. Finally, absorbed dose rate in air values were calculated from the naturally occurring radionuclide concentration in soils. The results showed good correspondence between the values obtained from ISGS and those obtained from laboratory determinations with the same soils.


Urinary incontinence-pathophysiology and management outline.
Urinary incontinence is common in the community and may impact significantly on quality of life; yet only one-third of sufferers seek medical attention. There are many treatment options for patients suffering with urinary incontinence. This article aims to aid general practitioners in the management urinary incontinence. We outline the pathophysiology of urinary incontinence in women and provide a primary care treatment paradigm. Suggestions for when specialist referral would be of benefit are also discussed. Most urinary incontinence can be evaluated and treated in the primary care setting after careful history and simple clinical assessment. Initial treatment, for both urge urinary incontinence and stress urinary incontinence, is lifestyle modification and pelvic floor muscle treatment. Urinary urgency responds to bladder training and pharmacotherapy with anticholinergic medication. Pharmacotherapy has a limited place in stress incontinence. If there is complex symptomatology or primary management fails, then referral to a specialist is suggested.


Gypenoside XVII inhibits ox-LDL-induced macrophage inflammatory responses and promotes cholesterol efflux through activating the miR-182-5p/HDAC9 signaling pathway.
The deposition of lipids in macrophages and the subsequent formation of foam cells significantly increase the risk of developing atherosclerosis (As). Targeting ATP-binding cassette transporter A1/G1 (ABCA1/ABCG1)-mediated reverse cholesterol transport is crucial for regulating foam cell formation. Therefore, the search for natural chemical components with the ability to regulate ABCA1/G1 is a potential drug target to combat the development of atherosclerosis. Gypenoside XVII (GP-17), a gypenoside monomer extracted from gynostemma pentaphyllum, presents an efficient anti-atherosclerosis function. However, the suppressed formation mechanism of foam cells by GP-17 remains elusive. To explore the protective activities of GP-17 in ox-LDL-induced THP-1 macrophage-derived foam cells through modulating the promotion of cholesterol efflux and alleviation of inflammation. MTT was used to detect cell viability. Bodipy493/503 and oil red O staining were performed to measure cell lipid deposition. Enzymatic assay was used to measure intracellular cholesterol measurement. Cholesterol efflux/uptake were determined by cholesterol efflux assay and Dil-ox-LDL uptake assay. Inflammatory cytokines were measured by ELISA. Bioinformatics prediction and dual luciferase reporter assay were performed to validate miR-182-5p targeting HDAC9. Relative protein levels were evaluated by immunoblotting and relative gene levels were determined by quantitative real-time PCR. Our results showed that GP-17 upregulated the expression of ABCA1, ABCG1 and miR-182-5p, but reduced HDAC9 expression levels in lipid-loaded macrophages, which promoted cholesterol efflux and inhibited lipid deposition. Additionally, GP-17 promoted the M2 phenotype of the macrophage and suppressed the inflammatory response in THP-1 macrophage-derived foam cells. Overexpression of HDAC9 or suppression of miR-182-5p eliminated the effects of ABCA1/G1 expression, lipid deposition and pro-inflammatory response. These findings suggest that GP-17 exerts a beneficial effect on macrophage lipid deposition and inflammation responses through activating the miR-182-5p/HDAC9 signaling pathway.