Tissue renin-angiotensin systems and reproduction.
The continued acquisition of information on the distribution of expression of components of the renin-angiotensin system shows that it has functions in the tissues that are quite unrelated to its systemic actions. In particular, both type 1 and type 2 angiotensin receptors are found in many tissues of the reproductive system of both sexes. In addition, the widespread occurrence of (pro)renin, angiotensin converting enzyme and angiotensinogen suggests that the generation of angiotensin II within the tissues occurs at sites close to its sites of action. The data suggest that angiotensin II operates as an important paracrine agent with profoundly significant roles in several functions of the reproductive system, and in fertility.


High-efficiency sample preparation approach to determine acrylamide levels in high-fat foods.
An improved sample preparation method was developed to enhance acrylamide recovery in high-fat foods. Prior to concentration, distilled deionized water was added to protect acrylamide from degradation, resulting in a higher acrylamide recovery rate from fried potato chips. A Chrome-Matrix C18 column (2.6 μm, 2.1 × 100 mm) was used for the first time to analyze acrylamide levels using ultra high performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry, displaying good separation of acrylamide from interference. A solid-phase extraction procedure was avoided, and an average recovery of >89.00% was achieved from different food matrices for three different acrylamide spiking levels. Good reproducibility was observed, with an intraday relative standard deviation of 0.04-2.38%, and an interday relative standard deviation of 2.34-3.26%. Thus, combining the improved sample preparation method for acrylamide analysis with the separation on a Chrome-Matrix C18 column (2.6 μm, 2.1 × 100 mm) using ultra high performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry is highly useful for analyzing acrylamide levels in complex food matrices.


Urinary Tract Infections among HIV-Positive Pregnant Women in Mwanza City, Tanzania, Are High and Predicted by Low CD4+ Count.
Introduction. Urinary tract infection (UTI) among pregnant women can lead to adverse maternal and foetal outcomes. UTI has been widely studied in the general obstetric population in Tanzania; the present study evaluated the magnitude, antimicrobial resistance, and predictors of UTI among HIV-positive pregnant women. Methods. Between March and May 2016 midstream urine samples from 234 women attending prevention of mother to child transmission of HIV (PMTCT) clinics were analyzed using standard methods. Data was analyzed by STATA version 11.0. Results. The prevalence of UTI was 21.4%, 50/234 [95% CI: 16.1-26.6]. The asymptomatically significant bacteriuria was higher than symptomatically significant bacteriuria (16.6% versus 4.7%, p < 0.001). On multivariable logistic regression analysis, single marital status (OR: 2.6, 95% CI: 1.1-6.1, and p = 0.026), low CD4+ counts of <200/μL (OR: 2.9, 95% CI: 1.1-7.7, and p = 0.031), and having UTI symptoms (OR: 2.5, 95% CI: 1.1-6.0, and p = 0.03) were independent predictors of UTI. Escherichia coli predominated (57.7%) and exhibited a low prevalence of resistance to nitrofurantoin (16.7%), gentamicin (10.0%), and ceftriaxone (13.3%). Four (13.3%) of these were extended-spectrum beta-lactamase producers. Conclusions. A considerable proportion of HIV-positive pregnant women in Mwanza have significant bacteriuria which calls for the need to introduce routine UTI screening at PMTCT clinics to guide specific treatment and prevent associated complications.


Effect of glucocorticoids on osteoclast function in a mouse model of bone necrosis.
Osteonecrosis, also termed aseptic necrosis, is the cellular death of bone components due to interruption of the blood supply. Glucocorticoid (GC) therapy is a common non-traumatic cause of osteonecrosis. However, the mechanism by which GCs induce osteonecrosis remains to be elucidated. The aim of the present study was to investigate the effects of GCs on osteoclast and osteoblast differentiation and function in a GC‑induced osteonecrosis mouse model. BALB/c male mice (n=40; 4‑weeks‑old) were treated with dexamethasone and asparaginase for 8 weeks. The control group (n=20) was administered normal saline. The results demonstrated that the GC-treated group had a lower mean weight compared with the control group. Morphologically, 16/37 (43%) mice demonstrated significant osteonecrotic lesions in the GC‑treated group. However, osteonecrotic lesions were not observed in the mice of the control group. Furthermore, immunohistochemistry demonstrated that the GC‑treated group had a higher level of osteoprotegerin compared with the control group, without any change in the expression of receptor activator of nuclear factor‑κB ligand. In addition, tartarate‑resistant acid-phosphatase staining demonstrated significantly decreased osteoclasts in the areas of bone destruction in the GCs-treated group. Furthermore, the present study demonstrated that GCs increased expression levels of osterix and osteocalcin, and decreased expression of matrix metallopeptidase‑9 to regulate the differentiation and function of osteoblasts and osteoclasts. The results of the present study suggested that GCs influence bone remolding resulting in decreased osteoclasts formation/differentiation. Therefore, regulating the differentiation and activity of the osteoclasts may be beneficial to the control and treatment of osteonecrosis.


Purification and Some Properties of a New Levanase from Bacillus sp. No. 71.
A levanase from Bacillus sp. was purified to a homogeneous state. The enzyme had a molecular weight of 135,000 and an isoelectric point of pH 4.7. The enzyme was most active at pH 6.0 and 40°C, stable from pH 6.0 to 10.0 for 20 hr of incubation at 4°C and up to 30°C for 30 min of incubation at pH 6.0. The enzyme activity was inhibited by Ag (+), Hg(2 +), Cu(2 +), Fe(3 +), Pb(2+), and p-chloromercuribenzoic acid. The enzyme hydrolyzed levan and phlein endowise to produce levanheptaose as a main product. The limit of hydrolysis of levan and phlein were 71% and 96%, respectively.


[Acyl-CoA synthetase activity of long-chain mono and dicarboxylic acid in beef liver preparations (author's transl)].
Higher omega-oxidation activities in the diabetic mammal and the starved one suggest that omega-oxidation mechanism plays an important role under these conditions. Dicarboxylic acid that is the final product of omega-oxidation can be metabolized further by beta-oxidation, subsequently, formation of succinyl-CoA and short-chain dicarboxylic acid might be increased in the liver. The physiological significance of omega-oxidation might consist in supplying the substrate of TCA cycle for utilization of acetyl-CoA and excreting the short-chain dicarboxylate in urine resulting in the decrease of ketone bodies in the blood, especially in diabetes and starvation. On the bases of these information, it is important to investigate the metabolism of dicarboxylic acids. Generally, fatty acids must be activated before they enter the metabolic pathway. By in vitro studies with rat liver homogenate, we have recently demonstrated that octadecaned-ioic acid must be activated by ATP-Mg2+ and CoA as monocarboxylic acid is. However, it has not been studied to compare the activity of acyl-CoA synthetase on mono and dicarboxylic acid. So, in this report, we assayed the activity of acyl-CoA synthetase in beef liver preparations using palmitic or hexadecanedioic acid (C1;16) as substrate. The results are as follows 1) Activation capacity of the supernatant of sonicated mitochondria was less than that of sonicated microsome for either palmitate or hexadecanedioate. 2) Activation capacity for hexadecanedioate was less than that for palmitate in both supernatant of sonicated mitochondria and that of sonicated microsome. 3) In our experiment, it might be suggested that the subcellular distribution of hexadecanedioate activation is almost identical with that of palmitate activation.


A direct nonchromatographic assay for 1-acyl-sn-glycerol-3-phosphate acyltransferase.
1-Acyl-sn-glycerol-3-phosphate acyltransferase (also called lysophosphatidic acid acyltransferase) which catalyzes the acylation of 1-acyl-sn-glycerol-3-phosphate to phosphatidic acid is generally assayed by the use of a radioactive substrate followed by a time-consuming chromatographic separation of substrate and product. We report a direct and highly sensitive nonchromatographic assay for this enzyme based on the ability of Escherichia coli alkaline phosphatase to dephosphorylate 1-acyl-sn-glycerol-3-phosphate but not phosphatidic acid. This selective hydrolysis coupled with the use of 32P-labeled 1-acyl-sn-glycerol-3-phosphate as substrate permits measurement of the product, 32P-labeled phosphatidic acid by solvent extraction or precipitation. We also report a series of enzymatic reactions for the efficient conversion of 32Pi to 32P-labeled 1-acyl-sn-glycerol-3-phosphate.


[The scientific revolution in medicine of last quarter of XIX - first half of XX centuries: New approaches to diagnostic and treatment of diseases].
The article considers changes in mass physician consciousness approaches to diagnostic and treatment of diseases occurred in the end of XIX-first half of XX centuries. It was the result of gaining a foothold in medicine of new view on organism as a procedural system and concepts of diseases as a complex feedback reaction of this system to unfavorable effect of environmental factors. It is demonstrated that the major change in diagnostic became refusal of traditional for XIX century orientation of diagnostic search exclusively on "clinical prediction of pathological picture" in favor of complex evaluation of state of ill person. The scale transformations in medical business affecting clinic of internal diseases and surgery disciplines resulted in that for the first time symptomatic therapy was replaced by comparatively effective ethiotropic and pathogenic treatment.


Persistent antipsychotic polypharmacy and excessive dosing in the community psychiatric treatment setting: a review of medication profiles in 435 Canadian outpatients.
The present study aimed (1) to determine the proportion of patients treated with persistent antipsychotic polypharmacy in an outpatient population and (2) to determine if persistent antipsychotic polypharmacy is associated with excessive dosing. Using a province-wide network that links all pharmacies in British Columbia, Canada, to a central set of data systems, we identified community mental health outpatients who had been treated with the same pharmacologic regimen for at least 90 days. Apart from antipsychotics, data collection included anticholinergics, antidepressants, mood stabilizers, benzodiazepines, lipid-lowering agents, and antidiabetic agents. Demographic data including sex, age, and diagnosis were obtained from the patient's chart. In order to compare dosages of the various antipsychotics we used a fixed unit of measurement based on dividing the prescribed daily dose (PDD) by the defined daily dose (DDD). A PDD/DDD ratio greater than 1.5 was defined as excessive dosing. Four hundred thirty-five patients met the inclusion criteria and were included in the analysis. Overall, the prevalence of persistent antipsychotic polypharmacy was 25.7% for the entire cohort. The prevalence of persistent antipsychotic polypharmacy was highest for patients with schizoaffective disorder (33.7%), followed by schizophrenia (31.7%), psychosis not otherwise specified (20.0%), bipolar disorder (16.9%), and major depression (14.3%). The mean +/- SD PDD/DDD ratio for all patients prescribed persistent antipsychotic polypharmacy was not only excessive, it was significantly greater compared to that of patients receiving antipsychotic monotherapy (1.94 +/- 0.12 vs 0.94 +/- 0.04, P < .005). Using a diagnostically heterogeneous outpatient population, this study is, we believe, the first to report that persistent antipsychotic polypharmacy is associated with excessive dosing, in and of itself as well as compared to antipsychotic monotherapy.


Free radical formation in crystals of guanine hydrochloride dihydrate: an ESR and ENDOR study.
Radiation-induced free radical formation in single crystals of guanine hydrochloride dihydrate has been studied at temperatures between 20 and 300 K using ESR and ENDOR spectroscopy. At low temperatures three radical species are trapped. Two of these are the C8 H-addition radical R1 previously analysed by Alexander and Gordy (1967) and the O6-protonated anion radical R2. The third species (R4) remains unidentified. Upon annealing at 280 K for an extended period the protonated anion R2 transforms into a new radical R3 which exhibit a well-defined hyperfine pattern but still could not be identified unambiguously. Also radical R4 probably transforms into a new radical (R5) upon such treatment. One proton coupling due to R5 was detected. A scheme of radical reactions incorporating these five radicals is proposed. This scheme also suggests that differences in radical formation between the monohydrate and dihydrate crystals of guanine hydrochloride depends upon differences in the hydrogen bonding network.


Host-dependent editing of SARS-CoV-2 in COVID-19 patients.
A common trait among RNA viruses is their high capability to acquire genetic variability due to viral and host mechanisms. Next-generation sequencing (NGS) analysis enables the deep study of the viral quasispecies in samples from infected individuals. In this study, the viral quasispecies complexity and single nucleotide polymorphisms of the SARS-CoV-2 spike gene of coronavirus disease 2019 (COVID-19) patients with mild or severe disease were investigated using next-generation sequencing (Illumina platform). SARS-CoV-2 spike variability was higher in patients with long-lasting infection. Most substitutions found were present at frequencies lower than 1%, and had an A → G or T → C pattern, consistent with variants caused by adenosine deaminase acting on RNA-1 (ADAR1). ADAR1 affected a small fraction of replicating genomes, but produced multiple, mainly non-synonymous mutations. ADAR1 editing during replication rather than the RNA-dependent RNA polymerase (nsp12) was the predominant mechanism generating SARS-CoV-2 genetic variability. However, the mutations produced are not fixed in the infected human population, suggesting that ADAR1 may have an antiviral role, whereas nsp12-induced mutations occurring in patients with high viremia and persistent infection are the main source of new SARS-CoV-2 variants.


Effects of miR-490-5p targeting CDK1 on proliferation and apoptosis of colon cancer cells via ERK signaling pathway.
The aim of this study was to investigate the effects of micro ribonucleic acid (miR)-490-5p on the proliferation and apoptosis of colon cancer cells, and to explore its potential mechanism. The mRNA expression of miR-490-5p in 30 pairs of colon cancer tissues and adjacent normal tissues was detected via reverse transcription-polymerase chain reaction (RT-PCR). Human colon cancer SW480 cell lines were cultured in vitro and divided into Control group and miR-490-5p overexpression group (miR-490-5p mimic group). The nonsense sequence and miR-490-5p mimic were transfected using liposome transfection technique into colon cancer cells in control group and miR-490-5p mimic group, respectively. Cell proliferation and apoptosis in each group were then observed. At the same time, the effect of miR-490-5p on the growth of colon cancer in vivo was explored using subcutaneous tumorigenesis assay. The protein expressions of extracellular signal-regulated kinase (ERK)1/2 signaling pathway and cyclin-dependent kinase 1 (CDK1) were determined via Western blotting. Furthermore, immunohistochemical staining was performed to verify the protein expression of CDK1 in vivo. The expression of miR-490-5p in colon cancer tissues was significantly lower than that in adjacent normal tissues (p<0.05). After transfection with miR-490-5p mimic in vitro, EdU staining and colony formation assay showed that the proliferation ability of SW480 cells was significantly weakened (p<0.05). Meanwhile, the number of colonies in miR-490-5p mimic group was markedly less than that in Control group (p<0.05). The results of Western blotting revealed that overexpression of miR-490-5p remarkably up-regulated the Bax/Bcl-2 and C-Caspase3/T-Caspase3 ratios in cancer cells (p<0.05). Subsequent results indicated that the subcutaneous tumorigenesis of colon cancer cells was markedly inhibited by overexpression of miR-490-5p (p<0.05). According to the results of Western blotting, the activation of ERK signaling pathway and the protein expression of CDK1 were significantly suppressed by overexpression of miR-490-5p (p<0.05). In vivo experiments further revealed that the protein expression of CDK1 in colon cancer tissues increased significantly (p<0.05). MiR-490-5p was found lowly expressed in colon cancer patients. In addition, overexpression of miR-490-5p inhibited the proliferation and promoted the apoptosis of colon cancer cells via down-regulating CDK1 both in vitro and in vivo.


Psychosocial aspects of cancer in adults: implications for teaching medical students.
This article addresses psychosocial aspects of cancer and the cancer patient that the authors feel are important to teach medical students. A section on understanding the cancer patient deals with patient psychosocial responses to a diagnosis of cancer. Loss of control, anger and guilt, fear of abandonment, fear of pain, psychiatric disorders, and psychosocial factors all need to be explored by the health care team. Interventions, such as education, support groups, environmental manipulation, or psychological counseling including imagery or relaxation have proved to be effective. Relaxation therapy can also help to counteract the side effects of chemotherapy such as anticipatory nausea and vomiting. An increasing openness about discussing dying and the development of hospices have resulted in improvements of the care of the dying patient and family. Family members should be involved in the care of the cancer patient and can support the patient by promoting autonomy and control and by encouraging communication and expression of feelings. The doctor-patient relationship is central, and is changing from a paternalistic model to one encouraging greater patient participation. In studying the behavior of physicians at Albany Medical College, the authors found that oncologists spend more time with patients with the poorest prognoses. Patient satisfaction with the relationship was found to be high. Students can be instructed in these psychosocial aspects of oncology by means of videotapes, role-playing, or patient presentations, and more importantly by using the physicians as a role model. Comprehensive care of the cancer patient necessitates the integration of psychosocial aspects of care into the overall assessment and management plan. This article reviews the psychosocial aspects of care of the adult cancer patient taught to second year medical students as part of a 42 hour course entitled "The Cellular Basis of Cancer Medicine" at Albany Medical College. The didactic material covered in this article is based on local clinical work and research endeavors with adult cancer patients and is included in the course syllabus given to the students. The students are divided into four small groups, each of which has one of four teaching experiences, each lasting for 2 hours. The psychosocial aspects of cancer is one of the small groups. This group, consisting of 32 students each, is taught by a medical oncologist and a behavioral scientist. Videotapes of interviews done with patients and/or live interviews with patients are used to highlight the material covered in the syllabus.(ABSTRACT TRUNCATED AT 400 WORDS)


Double cancer comprising malignant pleural mesothelioma and squamous cell carcinoma of the lung treated with radiotherapy: A case report.
Pleurectomy/decortication (P/D) is the surgical treatment of choice for early malignant mesothelioma, but it remains unclear whether radiotherapy along with P/D should be used as multimodal treatment for this disease. We herein present the case of a 76-year-old man with a history of asbestos exposure who was diagnosed with left-sided malignant pleural mesothelioma in February 2010. The patient underwent chemotherapy with a combination of cisplatin and pemetrexed and achieved stable disease, after which time he was kept under observation. A positron emission tomography/computed tomography scan performed in February 2011 revealed nodular shadows with fluorodeoxyglucose uptake in S3 of the left lung; using bronchoscopy, the patient was diagnosed with stage IIB (cT3N0M0) primary squamous cell carcinoma. Chemoradiotherapy with vinorelbine and 60 Gy/20 fr radiotherapy was performed, and a partial response was obtained, suggesting that the radiotherapy used to treat the carcinoma of the lung may have also helped control the disease activity of the pre-existing mesothelioma. The present case indicates the value of radiotherapy in the treatment of malignant mesothelioma. The aim of the present study was to examine the possibility of new multimodal treatments for mesothelioma, along with a discussion of the relevant literature.


Impact of heterogeneity-corrected dose calculation using a grid-based Boltzmann solver on breast and cervix cancer brachytherapy.
To analyze the impact of heterogeneity-corrected dose calculation on dosimetric quality parameters in gynecological and breast brachytherapy using Acuros, a grid-based Boltzmann equation solver (GBBS), and to evaluate the shielding effects of different cervix brachytherapy applicators. Calculations with TG-43 and Acuros were based on computed tomography (CT) retrospectively, for 10 cases of accelerated partial breast irradiation and 9 cervix cancer cases treated with tandem-ring applicators. Phantom CT-scans of different applicators (plastic and titanium) were acquired. For breast cases the V20Gyαβ3 to lung, the D0.1cm(3) , D1cm(3) , D2cm(3) to rib, the D0.1cm(3) , D1cm(3) , D10cm(3) to skin, and Dmax for all structures were reported. For cervix cases, the D0.1cm(3) , D2cm(3) to bladder, rectum and sigmoid, and the D50, D90, D98, V100 for the CTVHR were reported. For the phantom study, surrogates for target and organ at risk were created for a similar dose volume histogram (DVH) analysis. Absorbed dose and equivalent dose to 2 Gy fractionation (EQD2) were used for comparison. Calculations with TG-43 overestimated the dose for all dosimetric indices investigated. For breast, a decrease of ~8% was found for D10cm(3) to the skin and 5% for D2cm(3) to rib, resulting in a difference ~ -1.5 Gy EQD2 for overall treatment. Smaller effects were found for cervix cases with the plastic applicator, with up to -2% (-0.2 Gy EQD2) per fraction for organs at risk and -0.5% (-0.3 Gy EQD2) per fraction for CTVHR. The shielding effect of the titanium applicator resulted in a decrease of 2% for D2cm(3) to the organ at risk versus 0.7% for plastic. Lower doses were reported when calculating with Acuros compared to TG-43. Differences in dose parameters were larger in breast cases. A lower impact on clinical dose parameters was found for the cervix cases. Applicator material causes systematic shielding effects that can be taken into account.


Quality of Survivorship in a Rare Disease: Clinicofunctional Outcome and Physical Activity in an Observational Cohort Study of 618 Long-Term Survivors of Ewing Sarcoma.
Purpose Significantly improved survival rates in patients with Ewing sarcoma have raised interest in accessing the quality of long-term survivorship. In this study, subjective and objective measurement tools, preclassified as physical or mental scores, were used to assess clinicofunctional outcome and physical activity after intensive bone tumor treatment. Methods Long-term outcome of 618 survivors from consecutive Ewing sarcoma trials was assessed by the Toronto Extremity Salvage Score, Short-Form Health Survey (SF-36), Brief Symptom Inventory (BSI), and Rosenberg Self-Esteem Scale questionnaires and by the accelerometric StepWatch 3 Activity Monitor. Prospective measurements were correlated retrospectively with standardized primary trial data. Results were compared with 316 nonrandom healthy peers by using effect sizes ( d). Median observation time was 12.9 years from primary diagnosis (range, 3.7 to 31.2 years). Results Absolute subjective scores were moderate to good for survivors. Compared with control subjects, unfavorable outcome was shown on physical Toronto Extremity Salvage Score, SF-36 Physical Component Summary, and BSI-Somatization scales (| d| ≥ 0.50; P < .01), in contrast to SF-36 Mental Component Summary, BSI-Anxiety, BSI-Depression, and Rosenberg Self-Esteem Scale mental scales (| d| ≤ 0.31). Survivors were less active than control subjects, as demonstrated by a step count difference of 1,742 steps per day ( d = -0.43; P < .01); however, on average, the recommended level for an active lifestyle was achieved (≥ 10,000 steps). Location of pelvic tumor was the major inferior disease-specific prognostic factor in physical scores ( P < .01), whereas nondisease-specific inferior factors in questionnaires were older age and female sex ( P < .01). Conclusion Survivors of Ewing sarcoma apparently returned to a normal life with minor limitations. Observed reductions in physical scores should be a focus in future research to optimize treatment strategies to reduce a negative impact on the quality of survivorship.


The physio-biochemical characterization reflected different calcium utilization efficiency between the sensitive and tolerant peanut accessions under calcium deficiency.
Peanut yield in southern China is usually limited by calcium deficiency in soil. Most previous studies have found that small-seed varieties showed higher tolerance than large-seed varieties (e.g. Virginia type) under calcium deficiency, however, our preliminary research found that sensitive varieties also existed in small-seed counterparts. Few studies have been conducted to characterize low-calcium tolerance among small-seed germplasms with genetic diversity, and the differences in physiological characteristics between sensitive and tolerant varieties has not been reported yet. Thus, in order to better understand such differences, the current study firstly collected and characterized a diversity germplasm panel consisting of 50 small-seed peanut genotypes via a 2-year field trial, followed by the physiological characterization in sensitive (HN032) and tolerant (HN035) peanut genotypes under calcium deficiency. As a result, the adverse effects brought by calcium deficiency on calcium uptake and distribution in HN032 was much larger than HN035. In details, calcium uptake in the aboveground part (leaves and stems) was reduced by 16.17% and 33.66%, while in the underground part (roots and pods), it was reduced by 13.69% and 68.09% under calcium deficiency for HN035 and HN032, respectively; The calcium distribution rate in the pods of HN035 was 2.74 times higher than HN032. The utilization efficiency of calcium in the pods of HN035 was 1.68 and 1.37 times than that of HN032 under calcium deficiency and sufficiency, respectively. In addition, under calcium deficiency conditions, the activities of antioxidant enzymes SOD, POD, and CAT, as well as the MDA content, were significantly increased in the leaves of HN032, peanut yield was significantly reduced by 22.75%. However, there were no significant changes in the activities of antioxidant enzymes, MDA content, and peanut yield in HN035. Therefore, higher calcium absorption and utilization efficiency may be the key factors maintaining peanut yield in calcium-deficient conditions for tolerant genotypes. This study lays a solid foundation for selecting low-calcium tolerant varieties in future peanut breeding.


Risk assessment of N-nitrosodimethylamine formed endogenously after fish-with-vegetable meals.
The consumption of fish and nitrate-rich vegetables may lead to the formation of the genotoxic carcinogen N-nitrosodimethylamine (NDMA) in the stomach. To assess human cancer risk associated with this formation, a dynamic in vitro gastrointestinal model was used to simulate NDMA formation in the stomach after a fish + vegetable meal. The experimental results were combined with statistical modeling of Dutch food consumption data resulting in predicted exposures to endogenously formed NDMA in the population. The 95th percentile of the long-term exposure distribution was around 4 ng/kg-bw in young children and 0.4 ng/kg-bw in adults. By comparing this exposure with the Benchmark Dose Lower bound (BMDL) 10 for liver cancer in a chronic carcinogenicity study, a chronic margin of exposure (MOE) was calculated of 7000 and 73,000 for young children and adults. Furthermore, the long-term exposure distribution was combined with a dose-response analysis of the liver cancer incidence data to obtain a cancer risk distribution for the human population. The 95th percentile of that distribution was 6 x 10(-6) extra risk for 5-year-old children and 8 x 10(-7) for adults. The liver cancer data allowed for the analysis of the relationship between tumor incidence and time to tumor. For an extra risk of 10(-6), the decrease in time to tumor was conservatively estimated at 3.8 min in the rat, equivalent to 0.1 days in humans. We also combined acute exposure estimates with the BMDL10 from an acute carcinogenicity study for NDMA, resulting in an acute MOE of 110,000. We conclude that the combined consumption of fish and nitrate-rich vegetables appears to lead to marginal increases of additional cancer risk.


Squamous cell carcinoma of the body of the uterus.
A case of primary squamous cell carcinoma of the body of the uterus is reported. The number of authentic cases of this tumour which meet the rigid criteria referred to is extremely small. The histological findings are described in detail and some aetiological considerations are mentioned briefly. Certain special aspects of the diagnosis are discussed.


Treatment of patients with clinical T3 prostate cancer.
To describe and evaluate treatment alternatives for patients with clinical T3 prostate cancer. Literature review with main focus on recent studies in order to include the impact of prostate specific antigen (PSA). The possibility of using neoadjuvant/adjuvant hormonal therapy in combination with surgery or radiation was assessed. Results were related to life expectancy, tumour grade and serum PSA. M and N-staging is mandatory before treatment with curative intent. Watchful waiting is an option for selected patients but early hormonal therapy seems to offer some survival advantages. Standard 65-70Gy external beam radiation is not sufficient for these patients with extracapsular disease but better results are obtained with dose-escalation (beyond 70Gy) and/or adjuvant hormonal therapy. Radical prostatectomy may be an option for patients with long life expectancy and "early" tumours, neoadjuvant hormonal withdrawal is of no proven value. Patients with a long life expectancy should not be denied treatment with curative intent solely based on the finding of extracapsular disease.


Pharyngoesophageal stricture and fistula. Treatment by free jejunal graft.
Fifty-five patients with disorders of the pharynx or cervical esophagus requiring extensive ablative therapy were reconstructed by heterotopic autotransplantation of a segment of jejunum. Of these 55 patients, the overwhelming majority were treated for squamous cell carcinoma or the complications of combined radiation and operative therapy. There were six graft failures in the entire group of 55 patients for a transfer reliability of 90%. Three patients died in the perioperative period (5%). The purpose of this paper is to report on the treatment of a subset of these patients in whom fixed cicatricial stenosis of the gullet was the problem or in whom a radionecrotic cutaneous fistula existed. Fourteen such patients were treated, ten with stricture and four with fistula. Both patch grafts of on-lay segments and more routine circumferentially intact tubed segments of jejunum were used depending upon the nature of the defect. The youngest patient in this group was a 3-year-old juvenile diabetic with caustic stricture and the oldest was a 75-year-old man with fixed stricture following operation and radiation for cancer. Nine of ten and four of four anatomic reconstructions were successful in the stricture and fistula patients, respectively. All of these 13 patients with a neo- gullet of jejunum were able to handle secretions and liquids satisfactorily. Eleven patients were on a regular diet and had no discernible physiological impairment in alimentation. One patient had mild dysphagia and used a blenderized diet. One patient was able to swallow liquids only. In this patient the resection for tumor was so high and so extensive that the physiologic act of deglutition itself was impaired. There were no perioperative deaths, although one patient has succumbed to recurrent and metastatic carcinoma. When conventional treatment for stricture or fistula in the cervical alimentary tract has failed, reconstruction can be accomplished safely by free revascularized jejunal graft. Successful alimentation can be anticipated in all patients in whom the physiologic mechanism of deglutition itself is not drastically impaired.


Behavioral Profiles of Children With Williams Syndrome From Spain and the United States: Cross-Cultural Similarities and Differences.
To identify similarities and differences in the behavioral profile of children with Williams syndrome from Spain (n = 53) and the United States (n = 145), we asked parents of 6- to 14-year-olds with Williams syndrome to complete the Child Behavior Checklist 6-18. The distribution of raw scores was significantly higher for the Spanish sample than the American sample for all of the higher-order factors and half of both the empirically based and Diagnostic and Statistical Manual of Mental Disorders (DSM)-oriented scales. In contrast, analyses based on country-specific T-scores indicated that the distribution for the Spanish sample was significantly higher than for the American sample only on the Social Problems scale. No gender differences were found. Genetic and cultural influences on children's behavior and cultural influences on parental ratings of behavior are discussed.


Two Japanese CADASIL families exhibiting Notch3 mutation R75P not involving cysteine residue.
Most previously reported mutations in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) result in an odd number of cysteine residues within the epidermal growth factor (EGF)-like repeats in Notch3. We report here R75P mutation in two Japanese CADASIL families not directly involving cysteine residues located within the first EGF-like repeats. Probands in both families had repeated episodes of stroke, depression, dementia as well as T2 high-intensity lesions in the basal ganglia and periventricular white matter, but fewer white matter lesions in the temporal pole on MRI. These families provide new insights into the diagnosis and pathomechanisms of CADASIL.


Structural capabilities in small and medium-sized patient-centered medical homes.
1) Evaluate structural capabilities associated with the patient-centered medical home (PCMH) model in PCMH pilots in Colorado, Ohio, and Rhode Island; 2) evaluate changes in capabilities over 2 years in the Rhode Island pilot; and 3) evaluate facilitators and barriers to the adoption of capabilities. We assessed structural capabilities in the 30 pilot practices using a cross-sectional study design and examined changes over 2 years in 5 Rhode Island practices using a pre/post design. We used National Committee for Quality Assurance's Physician Practice Connections-Patient-Centered Medical Home (PPC/PCMH) accreditation survey data to measure capabilities. We stratified by high and low performance based on total score and by practice size. We analyzed change from baseline to 24 months for the Rhode Island practices. We analyzed qualitative data from interviews with practice leaders to identify facilitators and barriers to building capabilities. On average, practices scored 73 points (out of 100 points) for structural capabilities. High and low performers differed most on electronic prescribing, patient self-management, and care-management standards. Rhode Island practices averaged 42 points at baseline, and reached 90 points by the end of year 2. Some of the key facilitators that emerged were payment incentives, "transformation coaches," learning collaboratives, and data availability supporting performance management and quality improvement. Barriers to improvement included the extent of transformation required, technology shortcomings, slow cultural change, change fatigue, and lack of broader payment reform. For these early adopters, prevalence of structural capabilities was high, and performance was substantially improved for practices with initially lower capabilities. We conclude that building capabilities requires payment reform, attention to implementation, and cultural change.


[The interesting case from the pediatric polyclinic].
An eleven year old girl from Turkey was diagnosed to have a periodic fever syndrome. The diagnosis of familial mediterranean fever was made by molecular analysis of a mutation in the MEFV-Gen which codes for pyrin. The disease is well-known in the mediterranean area and belongs to the periodic fever syndromes. These syndromes are discussed for their differential diagnosis focused to childhood.


Effect of activated charcoal on the absorption of amiodarone.
1 The ability of activated charcoal to prevent the absorption of amiodarone was studied in 18 healthy volunteers, divided into three groups of six subjects. 2 All subjects were administered a single dose of 400 mg amiodarone; one group ingested the drug with water only (control) and the second with 25 g of activated charcoal as a water suspension. The subjects in the third group were given 25 g of charcoal immediately after the 1.5 h blood sample. 3 The extent of amiodarone absorption was reduced by about 98% by simultaneously administered charcoal (P less than 0.001); taking charcoal 1.5 h after amiodarone still resulted in a 50% reduction in amiodarone bioavailability (P less than 0.05). 4 These results indicate that activated charcoal should be effective in preventing amiodarone absorption in acute poisoning.


[The role of cytological studies in urology].
1100 patients with pathological findings of the prostate, urothelium and lymph-nodes underwent cytological examination with histological control. Prostatic cytology showed a sensitivity of 81% in detecting cancer. Through reassessment of originally false negative or only suspicious aspirates a specificity rate of 90% was achieved while the rate of unsatisfactory smears were doubled. In urothelial tumors evidence of lavage cytology was significantly higher than exfoliative cytology and depends on grading and staging of the tumor. Tumors with a low grade of malignancy were rarely detected cytologically. Topical chemotherapy seems to change the accuracy of cytological examinations because of the difficulty to separate malignancy associated cell changes from therapy induced cellular features. Transperitoneal aspiration cytology of retroperitoneal lymph-nodes has no evidence.


Marriage, Separation and Beyond: A Longitudinal Study of Families of Children with Intellectual and Developmental Disabilities in a Norwegian Context.
This study addresses family structure in families raising a child with disabilities in Norway. The aims are to add to the literature on termination of parental relationships and to explore family research topics that are rarely discussed in disability research, such as cohabitation versus marriage and repartnering. Longitudinal survey data on families of children with intellectual and developmental disabilities who were born 1993-1995 were compared with register data on all families of same-aged children (five waves 1999-2012). Parents of children with disabilities had slightly lower termination rates and formalized their partnerships earlier. Furthermore, the rate of repartnering among divorced/separated mothers of young children with disabilities was similar to that of other mothers but decreases later in the child's life course. Results support the view that findings diverge and are most likely dependent on context.


Alzheimer's disease skin fibroblasts selectively express a bradykinin signaling pathway mediating tau protein Ser phosphorylation.
Increased Ser phosphorylation of tau microtubule-associated protein in the brain is an early feature of Alzheimer's disease (AD) that precedes progression of the disease to frank neuronal disruption. We demonstrate that bradykinin (BK) B2 receptor activation leads to selective Ser phosphorylation of tau in skin fibroblasts from persons who have or will develop AD due to Presenilin 1 mutations or Trisomy 21, but not in skin fibroblasts from normal individuals at any age. The increased signal transduction in AD fibroblasts that culminates in tau Ser phosphorylation reflects modification of the G protein-coupled BK B2 receptors themselves. Both the BK B2 receptor modification and BK-mediated tau Ser phosphorylation are dependent on activation of protein kinase C and can be detected in fibroblasts from persons with Trisomy 21 two decades before the characteristic onset of AD. This dysregulated signaling cascade in AD may thus be expressed throughout life as an aberrant pathway in peripheral tissues more accessible than brain for molecular analysis. The sites of greatest BK B2 receptor expression in brain overlap with those areas displaying the earliest pathology in the course of AD, suggesting that BK receptor pathway dysfunction may be a molecular signature yielding information about the pathogenesis of AD.


Aggressive doxorubicin-containing regimen (prednisone, methotrexate, 5-FU, doxorubicin, and cyclophosphamide; PM-FAC) in disseminated estrogen receptor-negative breast cancer.
Twenty-seven women with disseminated estrogen receptor-negative breast cancer received an aggressive chemotherapy program of prednisone, methotrexate, 5-FU, doxorubicin, and cyclophosphamide. Responses were achieved in 21 of 26 (81%) evaluable patients, eight (31%) of whom had complete responses. The median survival was 17 months. Despite the favorable overall response and a significant number of complete responses, all patients eventually relapsed. Although most patients relapsed systematically, two relapsed initially in the CNS.


Decreased admission serum albumin level is an independent predictor of long-term mortality in hospital survivors of acute myocardial infarction. Soroka Acute Myocardial Infarction II (SAMI-II) project.
Decreased serum albumin level (SAL) was reported to be associated with increased risk of cardiovascular events and short term-mortality in patients with acute myocardial infarction (AMI). To evaluate the association between SAL and long-term mortality in AMI hospital survivors. Retrospective analysis of patients admitted in a tertiary medical center for AMI 2002-2012 and discharged alive. active infections, inflammatory diseases, significant liver or kidney failure, malignancy, ejection-fraction <20%, severe heart valvular-disease and missing SAL. SAL was categorized as following: <3.4, 3.4-3.7, 3.7-3.9, 3.9-4.1 and >4.1g/dL. The primary outcome was all-cause mortality for up-to 10-years post-AMI. Out of 12,535 patients, 8750 were included. Patients with reduced SAL were older, higher rate of women, increased prevalence of severe left ventricular dysfunction, chronic renal failure, diabetes mellitus and ST-elevation AMI, 3-vessel coronary artery disease, and in-hospital complications. While the prevalence of chronic ischemic coronary disease, dyslipidemia, smokers and obesity, was lower. Mortality rates throughout the follow-up period increased as SAL decreased with 17.6%, 24%, 28.5%, 38.6%, and 57.5% for SAL of >4.1, 3.9-4.1, 3.7-3.9, 3.4-3.7 and <3.4g/dL respectively (p-for-trend <0.001). Using the SAL category of >4.1g/dL as the reference group, Adjusted Hazard Ratio values were 1.14 (p=0.107), 1.23 (p=0.007), 1.39 (p<0.001) and 1.70 (p<0.001) for the SAL categories of 3.9-4.1, 3.7-3.9, 3.4-3.7 and <3.4g/dL respectively. Decreased SAL on admission, including levels within "normal" clinical range, is significantly associated with long-term all-cause mortality in hospital survivors of AMI with a "dose-response" type association.


Are farmers motivated to select for heat tolerance? Linking attitudinal factor, perceived climate change impact and social trust to farmers breeding desires.
This study provides an understanding of dairy farmers' willingness to include heat tolerance in the breeding goals and the modulating effect of socio-psychological factors and farm profile. A survey instrument including a choice experiment was designed to specifically address the trade-off between heat tolerance and milk production level. One hundred and 22 farmers, across cattle, goats and sheep farms were surveyed face-to-face. The results of the experiment show that most farmers perceive that heat stress and climate change are increasingly important problems, and that farming communities should invest more in generating knowledge and resources on mitigation strategies. However, we found limited initial support for selection for heat tolerance. This attitude changed when farmers were presented with objective information on the benefits and limitations of the different breeding choices, after which most farmers supported selection for heat tolerance but only if compromising milk production gains to a small extent. Our results show that farmers' selection choices are driven by the interactions between heat stress risk perception, attitudes toward breeding tools, social trust, the species reared and farm production level. In general, farmers willing to support selection of heat-tolerant animals are those with positive attitudes toward genetic values and genomic information and a strong perception of climate change and heat stress impact on farm. On the contrary, negative support for selection for heat tolerance is found among farmers with high milk production levels, high trust in farming magazines, livestock farmers associations, and veterinarians, and low trust in environmental and animalist groups.


A novel method for determining the phase of T-wave alternans: diagnostic and therapeutic implications.
T-wave alternans (TWA) has been implicated in the pathogenesis of ventricular arrhythmias and sudden cardiac death. However, to estimate and suppress TWA effectively, the phase of TWA must be accurately determined. We developed a method that computes the beat-by-beat integral of the T-wave morphology, over time points within the T-wave with positive alternans. Then, we estimated the signed derivative of the T-wave integral sequence, which allows the classification of each beat to a binary phase index. In animal studies, we found that this method was able to accurately identify the T-wave phase in artificially induced alternans (P<0.0001). The coherence of the phase increased consistently after acute ischemia induction in all body-surface and intracardiac leads (P<0.0001). Also, we developed a phase-resetting detection algorithm that enhances the diagnostic utility of TWA. We further established an algorithm that uses the phase of TWA to deliver appropriate polarity-pacing pulses (all interventions compared with baseline, P<0.0001 for alternans voltage; P<0.0001 for K(score)), to suppress TWA. Finally, we demonstrated that using the phase of TWA we can suppress spontaneous TWA during acute ischemia; 77.6% for alternans voltage (P<0.0001) and 92.5% for K(score) (P<0.0001). We developed a method to quantify the temporal variability of the TWA phase. This method is expected to enhance the utility of TWA in predicting ventricular arrhythmias and sudden cardiac death and raises the possibility of using upstream therapies to abort a ventricular tachyarrhythmia before its onset.


Removal of Soluble ACE2 in VeroE6 Cells by 17β-Estradiol Reduces SARS-CoV-2 Infectivity.
Women are less susceptible than men to coronavirus disease 2019 (COVID-19), which might be due to the female steroid hormone 17β-estradiol. We hypothesized that 17β-estradiol removes the soluble portion of angiotensin-converting enzyme 2 (sACE2) to which severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds in host cells and that sACE2 then binds to the virus, thereby reducing the infectivity. In the present study, VeroE6/serine protease 2 transmembrane protein (TMPRSS2) cells were infected with pseudo SARS-CoV-2 viruses and used as our model system. This infectivity was reduced by the application of 17β-estradiol. After applying 17β-estradiol to the VeroE6/TMPRSS2 cells, we used a sandwich enzyme-linked immunosorbent assay (ELISA) to measure the sACE2 concentration in the culture medium. Our findings revealed that 17β-estradiol removes sACE2 from VeroE6/TMPRSS2 cells. Furthermore, the pseudo SARS-CoV-2 viruses were incubated in culture medium with ACE2 collected from 17β-estradiol-treated VeroE6/TMPRSS2 cells, and the viruses were measured with an ultrasensitive ELISA using anti-spike protein antibodies. The amount of spike proteins decreased according to the concentration of 17β-estradiol applied. These results clearly demonstrated that the soluble portion of ACE2, which was removed from 17β-estradiol-treated VeroE6/TMPRSS2 cells, bound to the spike proteins of SARS-CoV-2, thereby reducing COVID-19 infectivity.


Rapamycin-induced phosphaturia.
The mammalian target of rapamycin (mTOR) is known to stimulate a variety of transport mechanisms including the intestinal phosphate transporter NaPi-IIb. The present study was performed to elucidate whether mTOR similarly regulates the major renal tubular phosphate transporter NaPi-IIa. To this end, NaPi-IIa was expressed in Xenopus oocytes with or without mTOR and phosphate transport estimated from phosphate-induced (1 mM) current (I(pi)). As a result, I(pi) was observed in NaPi-IIa-expressing but not in H(2)O-injected Xenopus oocytes. Co-expression of mTOR significantly enhanced I(pi) in NaPi-IIa-expressing Xenopus oocytes, an effect abrogated by treatment with rapamycin (50 nM for the last 24 h of incubation). In a second series of experiments, the effect of rapamycin was analysed in mice. The in vivo administration of rapamycin (3 microg/g body weight/day) for 3 days resulted in phosphaturia in mice despite a tendency of plasma phosphate concentration to decrease. mTOR contributes to the regulation of renal phosphate transport, and rapamycin thus influences phosphate balance.


Diet Versus Phylogeny: a Comparison of Gut Microbiota in Captive Colobine Monkey Species.
Both diet and host phylogeny shape the gut microbial community, and separating out the effects of these variables can be challenging. In this study, high-throughput sequencing was used to evaluate the impact of diet and phylogeny on the gut microbiota of nine colobine monkey species (N = 64 individuals). Colobines are leaf-eating monkeys that fare poorly in captivity-often exhibiting gastrointestinal (GI) problems. This study included eight Asian colobines (Rhinopithecus brelichi, Rhinopithecus roxellana, Rhinopithecus bieti, Pygathrix nemaeus, Nasalis larvatus, Trachypithecus francoisi, Trachypithecus auratus, and Trachypithecus vetulus) and one African colobine (Colobus guereza). Monkeys were housed at five different captive institutes: Panxi Wildlife Rescue Center (Guizhou, China), Beijing Zoo, Beijing Zoo Breeding Center, Singapore Zoo, and Singapore Zoo Primate Conservation Breeding Center. Captive diets varied widely between institutions, but within an institution, all colobine monkey species were fed nearly identical or identical diets. In addition, four monkey species were present at multiple captive institutes. This allowed us to parse the effects of diet and phylogeny in these captive colobines. Gut microbial communities clustered weakly by host species and strongly by diet, and overall, colobine phylogenetic relationships were not reflected in gut microbiota analyses. Core microbiota analyses also identified several key taxa-including microbes within the Ruminococcaceae and Lachnospiraceae families-that were shared by over 90% of the monkeys in this study. Microbial species within these families include many butyrate producers that are important for GI health. These results highlight the importance of diet in captive colobines.


Development of seven secondary neoplasms in a nevus sebaceous: a case report and literature review.
Nevus sebaceous of Jadassohn is a congenital cutaneous hamartoma with epidermal, sebaceous, follicular, and apocrine structures that usually appears at birth or in early childhood. It has the potential to generate a variety of secondary neoplasms of different lineages, and the risk increases with patient age. Although multiple neoplasms may occasionally arise within the same lesion, the coexistence of more than five secondary tumors is extremely rare. Here we report a case of seven secondary tumors including syringocystadenoma papilliferum, desmoplastic trichilemmoma, sebaceoma, trichoblastoma, pigmented trichoblastoma, sebaceous adenoma, and tumor of follicular infundibulum arising within a nevus sebaceous. The complete diagnosis relies on the histopathological analysis of multipoint biopsies and delicate pathological sections.


Education aimed at increasing international collaboration and decreasing inequalities.
Educational initiatives in cancer research have to align with the needs of patients, individuals at risk, healthcare systems and public health organisations. The above interests demand strong translational interactions between basic research, clinical/prevention research and entrepreneurship. The resulting synergy between these three entities is expected to stimulate identification of unresolved issues in cancer biology, as well as unmet needs in diagnostics, treatment and prevention. It will also encourage the development of international research collaborations and, in turn, improve access to innovative research infrastructures. Education and dissemination of knowledge and technologies must be a cornerstone of any future European mission-oriented approach to cancer, as it will ensure that new cancer treatments reach all patients within the European Union, and also help reduce gross inequalities in cancer incidence and mortality. A large number of educational institutions ranging from local universities to pan-European organisations have developed excellent educational activities. However, a cancer mission will highlight additional roles for higher education that will complement and provide novel approaches. Educational and training activities should target the general public (dissemination) for primary cancer prevention, as well as the next generation of cancer researchers in basic and clinical research all over Europe. The experiences of patients are also needed to improve health-related quality-of-life and outcomes research. A mission approach to cancer would enhance the exchange of researchers within Europe and worldwide, and prioritise collaborations between Western/Central and Eastern Europe countries. The Comprehensive Cancer Centres (CCCs) will be crucial to train scientific staff in established centres as well as in candidate centres aspiring to join networks of CCCs. In addition, CCCs will have an important role to play by offering educational programmes for the next generation of clinical/research leaders.


Non-Thermal Supercritical Carbon Dioxide Processing Retains the Quality Parameters and Improves the Kinetic Stability of an Araticum Beverage Enriched with Inulin-Type Dietary Fibers.
Fruit-based beverages have been considered excellent food vehicles for delivering prebiotics. However, the conventional thermal processes currently used to microbiologically and enzymatically stabilize these products may cause significant losses in their sensory, physicochemical, nutritional, and bioactive characteristics. Thus, in this study, we evaluate the effect of different levels of pressure (8, 15, and 21 MPa) and temperature (35 and 55 °C) on the characteristics of an inulin-enriched araticum beverage processed with non-thermal supercritical carbon dioxide (SC-CO2) technology. The temperature showed a significant effect on total soluble solids, pH, particle size distribution, and kinetic stability. In contrast, pressure affected only the particle size distribution. The interaction between pressure and temperature influenced the total soluble solids, pH, and particle size distribution. Color parameters, ζ-potential, and glucose and fructose contents were not modified after all SC-CO2 treatments. Moreover, the SC-CO2 treatments preserved the inulin molecular structure, thus maintaining its prebiotic functionality. Overall, the SC-CO2 treatment did not alter the sensory, nutritional, and functional quality of the beverage, while improving its physical stability during storage. Therefore, non-thermal SC-CO2 treatment can be an alternative to current conventional processes for stabilizing inulin-enriched fruit-based beverages.


A case of pulmonary nodules in a patient living with HIV diagnosed with secondary syphilis.
We discuss a case of secondary syphilis with pulmonary involvement in a 45-year-old man who tested positive for HIV. He presented with dyspnoea, chest pain and a rash on his limbs and torso. A CT showed multiple bilateral necrotic lung nodules. A diagnosis of pulmonary syphilis was made due to his respiratory symptoms and imaging, his serological, histopathology findings, and the resolution of symptoms on treatment with benzathine penicillin.


[Focus on popular science education of glaucoma and reduce glaucomatous low vision and blindness].
The prevention of blindness caused by glaucoma is a difficult task. In order to accomplish the task better, we need the participation of whole society and popularize relevant medical knowledge. Popular science and related knowledge of glaucoma are needed to the people especially for high risk population. If people know glaucoma better and actively join the screening of glaucoma, we can find and diagnose glaucoma earlier, avoid late treatment and reduce the glaucomatous visual function impairment. For patients who had been diagnosed with glaucoma, they should aware and accept new medical concept and technique through systemic popular science education. They should actively participate the whole procedure of the disease management and improve their compliance and confidence. Academic organization of ophthalmology should participate and guide the patient education, improve the individualized comprehensive health care for the diagnosis and treatment and third-order health care system that is suitable for the condition of our country, help improving the prognosis of glaucoma and life quality related to vision for advanced and late glaucoma. (Chin J Ophthalmol, 2017, 53: 81-84).


Latin America and the Caribbean Code Against Cancer 1st edition: Tobacco and nicotine-related products, secondhand smoke, and alcohol and cancer.
Tobacco, secondhand smoke (SHS), and alcohol, all carcinogens, are leading preventable cancer risk factors in Latin America and the Caribbean (LAC). Since 2000, smoking and SHS exposure have significantly decreased in the region. Yet alcohol consumption remains high. The entry of nicotine-related products such as electronic cigarettes (e-cigs) threatens achievements made in tobacco control and chronic diseases prevention, including cancer. E-cigs use is likely associated with smoking initiation among adolescents who had never smoked and dual use with combustible tobacco products. Therefore, the LAC Code Against Cancer recommends to the public actions they can take to reduce their risk of cancer: 1. Don't smoke or use any type of tobacco. If you do, quitting is possible, with professional help if needed. Don't use e-cigarettes either, as they lead to tobacco use. 2. Make your home a smoke-free place. Respect and promote laws that ensure smoke-free spaces to protect our health. and 3. Avoid drinking alcoholic beverages. This helps prevent several types of cancer. The Code recommends to policymakers a package of cost-effective policies based on the MPOWER and SAFER to prevent cancer at the population level. It also recommends that primary care health professionals: 1. Ask all their patients and their families whether they smoke or vape, inform them about the harms of smoking and vaping, and promote tobacco and nicotine related products cessation strategies among users. 2. Inform about the harms of exposure to SHS, especially among children, and promote smoke-free environments, and 3. Prevent alcohol use by their patients and their families, use tools to assess use, intensity, and frequency, and apply brief counseling intervention to support alcohol abstinence in primary care.


Reduced Mortality in Severely Injured Patients Using Hospital-based Helicopter Emergency Medical Services in Interhospital Transport.
Recent evidence has demonstrated the survival benefits of helicopter transport for trauma patients. The purpose of this study was to evaluate the effectiveness of hospital-based helicopter emergency medical services (H-HEMS) in comparison with ground ambulance transport in improving mortality outcomes in patients with major trauma. Study participants were divided into 2 groups according to type of transport to the trauma center; that is, either via ground emergency medical services (GEMS) or via H-HEMS. The study was conducted from October 2013 to July 2015. Mortality outcomes in the H-HEMS group were compared with those in the GEMS group by using the Trauma and Injury Severity Score (TRISS) analysis. The number of participants finally included in the study was 312. Among these patients, 63 were adult major trauma patients transported via H-HEMS, and 47.6% were involved in traffic accidents. For interhospital transport, the Z and W statistics revealed significantly higher scores in the H-HEMS group than in the GEMS group (Z statistic, 2.02 vs. 1.16; P = 0.043 vs. 0.246; W statistic, 8.87 vs. 2.85), and 6.02 more patients could be saved per 100 patients when H-HEMS was used for transportation. TRISS analysis revealed that the use of H-HEMS for transporting adult major trauma patients was associated with significantly improved survival compared to the use of GEMS.


The SHOOT ORGANIZATION2 gene coordinates leaf domain development along the central-marginal axis in rice.
We describe how rice leaves are regionalized and regulated along the central-marginal axis. The shoot organization2 (sho2) mutant, a weak allele of SHOOTLESS4 that is a ZIPPY/ARGONAUTE7 homolog in rice, shows a variety of leaf abnormalities; filamentous leaves, bi- or trifurcated leaves, separation of the filamentous structure from the leaf blade or deletion of the margin. All of these phenotypes can be interpreted as combinatorial defects in the growth of the central, lateral and marginal domains along the central-marginal axis, on the condition that the growth of the central domain is predominant. The leaf founder cells for the lateral and marginal domains are recruited normally in sho2, indicating that sho2 is defective in the growth of leaf domains after the founder cells are recruited. The expression pattern of SHO2 in the outer layer of the shoot apical meristem and the adaxial surface of the leaf, as well as the altered expression of HD-ZIP III and ETTIN homologs in the central domain of sho2 leaves, suggest that normal development of the central domain is a prerequisite for the synchronous growth of the three domains. This synchrony is thought to be mediated by a small interfering RNA-dependent process.


Effect of hormonal manipulation using clomiphene citrate prior to microdissection testicular sperm retrieval.
Microdissection Testicular Sperm Extraction (micro-TESE) is a surgical method used for retrieving sperm from men with non-obstructive azoospermia. Clomiphene citrate (CC) is a selective estrogen receptor modulator (SERM) that stimulates luteinizing hormone (LH) and follicle-stimulating hormone (FSH) production. It is believed that treating patients with CC prior to micro-TESE increases the chance of sperm retrieval. This retrospective study was conducted in a tertiary care center in Riyadh, Saudi Arabia and included all patients who underwent Micro-TESE from August 2015 to November 2018. Data related to the pre-surgery hormonal levels, testicular volume, and associated genetic abnormalities were collected. chi-square and t-test were used to compare variables. A p-value of less than 0.05 was considered significant. A total of 122 patients were included in this study, with 30.0% (n=37) treated with CC. The overall sperm retrieval rate was 44.3%. Micro-TESE results were not statistically affected by age, testosterone levels, Klinefelter syndrome, or taking CC. However, higher testicular volumes and lower LH and FSH levels had more positive micro-TESE results. In conclusion, Micro-TESE results were not affected by CC, age or testicular volume.


Accuracy of several cervical screening strategies for early detection of cervical cancer: a meta-analysis.
The objectives of this study were to assess the accuracy of 6 common cervical screening strategies, including visual inspection with acetic acid, with a magnifying device, or with Lugol iodine (VILI), human papillomavirus testing with Hybrid Capture 2 assay, conventional Papanicolaou smear, and thin liquid-based cytology (LBC), and then to compare data obtained by the aforementioned 6 strategies. PubMed, EMBASE, and The Cochrane Library were systematically searched for all original relevant studies about early detection of cervical cancer. A meta-analysis was performed to evaluate the accuracy of the 6 screening strategies covering sensitivity, specificity, diagnostic odds ratio, and the area under the receiver operating characteristic curve. Fifteen articles containing 22 cross-sectional studies were finally identified. The combined estimates of sensitivity for visual inspection with acetic acid, magnified visual inspection with acetic acid, VILI, Hybrid Capture 2 assay, conventional Papanicolaou smear, and LBC were 77%, 64%, 91%, 74%, 59%, and 88%, respectively; the combined values of specificity of these screening strategies were 87%, 86%, 85%, 92%, 94%, and 88%, respectively; the diagnostic odds ratio were 22.43, 10.30, 57.44, 33.26, 22.49, and 51.56, respectively; and the area under the receiver operating characteristic curve were 0.8918, 0.7737, 0.9365, 0.9486, 0.9079, and 0.9418, respectively. This meta-analysis suggests that LBC appeared to be promising in primary cervical cancer screening in resourced regions, and VILI might be a good choice to identify/exclude cervical cancerous and precancerous lesions in resource-constrained regions.


Tissue-type plasminogen activator (t-PA) lysis of aortic and mitral valve thrombosis.
Valve thrombosis is one of the most serious complications after prosthetic valve replacement. We report the use of tissue-type plasminogen activator (t-PA) in the treatment of a patient with thrombosed aortic and mitral valves. Thrombolysis resulted in immediate hemodynamic improvement and resolution of congestive heart failure, thereby avoiding surgical intervention. Based on our experience, thrombolysis with t-PA is an effective alternative in the treatment of thrombosed prosthetic valves.


Treatment of anaerobic infections with metronidazole.
The results of treatment of 10 patients with anaerobic infections with metronidazole are presented. Six patients were cured, three showed initial good response but circumstances required a change to another drug, and one patient did not respond. The unique spectrum of the drug, its pharmacology, and limitations are discussed. The results indicate that further clinical trials to determine the efficacy of metronidazole in the treatment of anerobic infections are indicated.


Use of commercial record linkage software and vital statistics to identify patient deaths.
We evaluate the ability of a microcomputer program (Automatch) to link patient records in our hospital's database (N = 253,836) with mortality files from California (N = 1,312,779) and the U.S. Social Security Administration (N = 13,341,581). We linked 96.5% of 3,448 in-hospital deaths, 99.3% for patients with social security numbers. None of 14,073 patients known to be alive (because they were subsequently admitted) was linked with California deaths, and only 6 (0.1%) of 6,444 were falsely identified as dead in the United States file. For patients with unknown vital status but items in the database likely to be associated with high 3-year mortality rates, we identified death records of 88% of 494 patients with cancer metastatic to the liver, 84% of 164 patients with pancreatic cancer, and 91% of 126 patients with CD4 counts of less than 50. Hospital data can be accurately linked with state and national vital statistics using commercial record linkage software.


Evolution of Acinetobacter baumannii In Vivo: International Clone II, More Resistance to Ceftazidime, Mutation in ptk.
Acinetobacter baumannii is an important nosocomial pathogen worldwide. A more comprehensive understanding of the within-host genomic evolution of A. baumannii would provide a molecule basis for improving treatment of A. baumannii infection. To understand the evolutionary mechanism facilitating A. baumannii survived in human body, we here reported the genomic analysis of A. baumannii isolated sampled from Chinese patients. We used whole-genome sequence of A. baumannii isolates from the same patient to determine single-nucleotide variants, insertion sequence mapping, and gene change. The MICs for 10 antimicrobial agents were determined. Motility assay and microscopy were performed on the isolated pairs harboring ptk mutations. The gene ptk encoded a putative protein tyrosine kinase involved in the production of capsular polysaccharide. Approximately half (39/86) of the strains isolated from the same patient harbored the same MLST patterns, and during the replacement of international clonal lineage II (ICL-II) and non-ICL-II strains, most of the alteration was that non-ICL-II strain was replaced by ICL-II strain (10/12). A. baumannii was resistant to major antimicrobial agents, whereas the strains were more resistant to ceftazidime, azithromycin, and sulfonamides after within-host evolution. Isolates from the ICL-II lineage displayed greater resistance to antimicrobial agents than non-ICL-II isolates. Isolates from ICL-II harbored more resistance genes and mobile elements than non-ICL-II strains. Several lineages evolved a more mucoid phenotype. Genome sequencing revealed that the phenotype was achieved by genetic changes in the ptk gene. ICL-II (especially ST195 and ST208) was the terminal destination for bacteria after within-host evolution. These results indicate that the molecular basis and the treatment for ICL-II strains needed further investigation.


Transactivation of the human keratin 4 and Epstein-Barr virus ED-L2 promoters by gut-enriched Krüppel-like factor.
The Krüppel-like family of transcription factors comprises genes that appear to have tissue-restricted functions. Expression of gut-enriched Krüppel-like factor (GKLF) may be important in the switch from proliferation to differentiation in the squamous epithelium. We sought to determine transcriptionally mediated effects of GKLF on two promoters active in the esophageal squamous epithelium, namely the Epstein-Barr virus ED-L2 and human keratin 4 promoters. Both promoters contain a CACCC-like motif previously shown to bind GKLF. To determine whether GKLF regulates genes containing this element, we first demonstrated expression and then cloned the full-length human GKLF from an esophageal squamous carcinoma cell line. In a transient transfection system, GKLF increased the activity of both promoters >25-fold, localized to regions containing the CACCC-like element. Recombinant GKLF specifically binds the CACCC-like motif in both promoters. GKLF epitope-tagged protein leads to the formation of two proteins of 65 and 34 kDa. The chromatographically purified 65-kDa protein binds the CACCC-like element from both Epstein-Barr virus ED-L2 and keratin 4 promoters, which is not attenuated by the 34-kDa protein. In summary, GKLF is expressed in esophageal squamous epithelial cells and transcriptionally activates two esophageal epithelial promoters important at the transition toward differentiation.


Epstein Barr virus in Argentine pediatric Hodgkin's disease.
Since Hodgkin's disease (HD) is an heterogeneous condition with diverse histological and epidemiological subgroups, it seemed worthwhile to investigate the Argentine pediatric pattern. Moreover, the presence of Epstein Barr virus (EBV) infection occurs at different ages depending on the development status of the country. Thus, it was interesting to assess the relation between EBV and HD in the Argentine pediatric population. The age distribution profile of our pediatric HD patients showed a peak in early childhood which declined towards adolescence, closely resembling EBV infection pattern. Male:female ratio of the studied population was 3.2:1 and the histological subtype distribution disclosed that mixed cellularity HD (MCHD) was the most common, an epidemiological profile shared with other developing countries. Fifty percent of assessed HD cases were associated with EBV, showing a significantly higher prevalence in the 3-6 years-old group, indicating a non-random distribution. EBV was also present in most of MCHD cases and in some nodular lymphocyte predominance HD (nLPHD) but entirely absent in nodular sclerosis HD (NSHD). Both EBV subtypes, namely EBV-1 and EBV-2, were detected in studied HD cases. EBV-HD association in the Argentine pediatric population reveals typical epidemiological features indicating EBV as the aetiologic agent or, alternatively as a cofactor in a considerable percentage of such HD cases.


Ocular sodium cromoglycate. An overview of its therapeutic efficacy in allergic eye disease.
Sodium cromoglycate stabilizes mast cell membranes and prevents the release of histamine and other biochemical mediators. When topically applied to the eye before allergen exposure, ocular sodium cromoglycate prevents many of the signs and symptoms associated with type I allergic reactions (which includes hayfever, acute allergic and chronic allergic conjunctivitis, and vernal keratoconjunctivitis) and giant papillary conjunctivitis. Although difficulties exist in evaluating clinical trials in allergic eye disease, both open and controlled studies have shown ocular sodium cromoglycate to be very effective in relieving the subjective symptoms and clinical signs of the above ocular disorders. In addition, ocular sodium cromoglycate may decrease the need for supplementary oral antihistamines and, more importantly, the need for ocular corticosteroids, thus decreasing the incidence of steroid-induced ocular side effects. However, in severe cases and in instances of acute exacerbation of symptoms, the combined ocular application of sodium cromoglycate and corticosteroids may be very effective. No systemic or severe adverse reactions have been attributed to ocular sodium cromoglycate, which is not surprising since systemic drug absorption from the eye is minimal. However, transient local stinging and burning have been reported. Thus, although further studies in giant papillary conjunctivitis and comparative studies with corticosteroids in allergic conjunctivitis and vernal keratoconjunctivitis are needed to more clearly define the extent of benefits that may be obtained from ocular sodium cromoglycate, it is clear that the safety and efficacy of the drug in type I allergic eye diseases is such that it should be considered as a first-line agent when drug therapy of these disorders is indicated.


Tenofovir-based alternate therapies for chronic hepatitis B patients with partial virological response to entecavir.
Entecavir (ETV) is a first-line antiviral therapy for treating chronic hepatitis B (CHB); however, some patients have suboptimal response to ETV. Currently, there are limited data on how to approach these patients. Therefore, our aim was to compare the effectiveness of two alternate therapies--tenofovir (TDF) monotherapy and combination therapy of ETV+TDF--in CHB patients with ETV partial virological response. We conducted a retrospective study of 68 patients who had partial virological response to ETV, defined as having detectable HBV DNA following at least 12 months of ETV, and were switched to TDF monotherapy (n = 25) or ETV+TDF (n = 43). Patients were seen in seven US liver/community-based clinics and started on ETV between 2005 and 2009. The majority of patients were male; the vast majority were Asian and had positive hepatitis B e antigen (HBeAg). Patients in both groups had similar pretreatment characteristics. Complete viral suppression (CVS) rates with TDF monotherapy and ETV+TDF were similar after 6 months (71% vs 83%, P = 0.23) and 12 months (86% vs 84%, P = 0.85), and there was no statistically significant difference in CVS rates even when only patients with higher HBV DNA levels at switch (>1000 IU/mL) were evaluated. Multivariate analysis indicated that ETV+TDF was not an independent predictor of CVS compared to TDF monotherapy (OR = 1.19, P = 0.63). In conclusion, TDF monotherapy and ETV+TDF are comparable in achieving CVS in CHB patients with partial virological response to ETV. Long-term alternate therapy with one pill (TDF monotherapy) vs two pills (ETV+TDF) could lead to lower nonadherence rates and better treatment outcomes.


An active avoidance behavioral paradigm for use in a mild closed head model of traumatic brain injury in mice.
A mild traumatic brain injury (TBI) occurs to millions of people each year. Translational approaches to understanding the pathogenesis of neurological diseases and the testing of the effectiveness of interventions typically require cognitive function assays in rodents. Our goal was to validate the active avoidance task using the GEMINI avoidance system in a mouse model of mild closed head injury (CHI). We found that shock intensity had only a marginal effect on the test. We found that sex was an important biological variable, as female mice learned the task better than male mice. We demonstrate that a single mild CHI in mice caused deficits in the task at four weeks post-injury. Active avoidance is a classical conditioning test in which mice must pair the presence of a conditioned stimulus with moving between two chambers to avoid an electric shock. External conditions (i.e., apparatus), as well as inherent differences in the mice, which may not be directly linked to the model of the disease (i.e., sensory differences), can affect the reproducibility of a behavioral assay. Before our study, there was a lack of standard operating procedures and validated methods for the active avoidance behavior for phenotyping mouse models of injury and disease. We offer a method for validating the active avoidance test, and a standard operating procedure, which will be useful in other models of neurological injury and disease.


Association between right-to-left shunts and brain lesions in sport divers.
Recent studies suggest that healthy sport divers may develop clinically silent brain damage, based on the association between a finding of multiple brain lesions on MRI and the presence of right-to-left shunt, a pathway for venous gas bubbles to enter the arterial system. We performed echocontrast transcranial Doppler sonography in 42 sport divers to determine the presence of a right-to-left shunt. Cranial MRI was carried out using a 1.5 T magnet. A lesion was counted if it was hyperintense on both T2-weighted and T2-weighted fluid attenuated inversion recovery sequences. To test the hypothesis that the occurrence of postdive arterial gas emboli is related to brain lesions on MRI, we measured postdive intravascular bubbles in a subset of 15 divers 30 min after open water scuba dives. Echocontrast transcranial Doppler sonography revealed a right-to-left shunt in 16 of the divers (38%). Only one hyperintensive lesion of the central white matter was found and that was in a diver with no evidence of a right-to-left shunt. Postdive arterial gas emboli were detected in 3 out of 15 divers; they had a right-to-left shunt, but no pathologic findings on cranial magnetic resonance imaging. Our data support the theory that right-to-left shunts can serve as a pathway for venous gas bubbles into the arterial circulation. However, we could not confirm an association between brain lesions and the presence of a right-to-left shunt in sport divers.


Genetic diversity among clinical isolates of Candida glabrata analyzed by randomly amplified polymorphic DNA and multilocus enzyme electrophoresis analyses.
The genetic diversity of 47 clinical and reference strains of Candida glabrata from several geographical origins and diverse clinical disorders, with different antifungal susceptibilities, as well as their genetic relationships were studied through multilocus enzyme electrophoresis (MLEE) and randomly amplified polymorphic DNA (RAPD) techniques. The genetic diversity estimated for 11 MLEE loci measured as average heterozygosity (h) was 0.055. A high level of genetic relatedness among isolates was established by cluster analysis. Forty-nine RAPD markers were analyzed, and the average genetic diversity among isolates, estimated by Shannon's index (Ho), was 0.372. The PhiST values estimated through an analysis of molecular variance to assess genetic differentiation among isolates revealed no genetic differentiation among them. Our results revealed very low genetic diversity among isolates, a lack of differentiation, and no association with their geographic origin and the clinical characteristics.


Draft Genome Sequence of Gephyronic Acid Producer Cystobacter violaceus Strain Cb vi76.
A draft genome sequence of Cystobacter violaceus strain Cb vi76, which produces the eukaryotic protein synthesis inhibitor gephyronic acid, has been obtained. The genome contains numerous predicted secondary metabolite clusters, including the gephyronic acid biosynthetic pathway. This genome will contribute to the investigation of secondary metabolism in other Cystobacter strains.


One Health Evaluation of Antimicrobial Use and Resistance Surveillance: A Novel Tool for Evaluating Integrated, One Health Antimicrobial Resistance and Antimicrobial Use Surveillance Programs.
We describe the development, application and utility of our novel, One Health Evaluation of Antimicrobial Use and Resistance Surveillance (OHE-AMURS) tool that we created to evaluate progress toward integrated, One Health surveillance of antimicrobial resistance (AMR) and antimicrobial use (AMU) as a complex system in Canada. We conducted a qualitative inquiry into the current state of policy and programs for integrated AMR/AMU surveillance using explicit and tacit knowledge. To assess the "messy" state of public health surveillance program development, we synthesized recommendations from previous reports by the National Collaborating Centre for Infectious Diseases and the Canadian Council of Chief Veterinary Officers; conducted an environmental scan to find all federal, provincial, and territorial AMR/AMU surveillance programs in Canada; and conducted semi-structured interviews with Canadian subject matter experts. To integrate evidence from these different sources we adapted two published tools to create a new evaluation matrix, deriving 36 components of the ideal integrated AMR/AMU surveillance system. Our two-way matrix tool allowed us to examine seven common, foundational elements of sustainable programs for each component, and assign a stage of development/sustainability ranking for each component according to the matrix definitions. Our adaptable novel tool allowed for granular and repeatable assessment of the many components of a complex surveillance system. The assessment proved robust and exacting to ensure transparency in our methods and results. The matrix allows flexible assignment of program components based on program principles, and stages can be adapted to evaluate any aspect of an AMR/AMU surveillance or other multi-faceted, multi-jurisdictional system. Future refinement should include an assessment of the scope of surveillance components.


Meal frequency and plasma lipids and lipoproteins.
Epidemiological data suggesting benefits of increased meal frequency on CHD risk and lipid and lipoprotein levels may be flawed because of biases associated with the method of data collection. In normolipidaemic individuals increasing meal frequency from three to six or more meals daily over a period of several weeks appears to be associated with reduced levels of total and LDL-cholesterol, possibly due to reduced cholesterol synthesis or enhancement of reverse cholesterol transport. However, in non-obese individuals with polygenic hyperlipidaemia and non-insulin-dependent diabetes, altered meal frequency does not appear to confer similar benefits. The reasons for the different responses in these groups of subjects is not clear. The reported effects of altered meal frequency on diurnal levels of triacylglycerols and fatty acids are more variable, with benefits being reported principally in association with meal frequencies exceeding those which might be translated into practical recommendations. Present data preclude recommendations concerning meal frequency on the basis of effects on lipids and lipoproteins. Even in healthy individuals amongst whom benefits have been observed, the periods of observation have been relatively short and it is not known whether adaptation occurs. Further research should focus on longer-term studies in healthy individuals as well as hyperinsulinaemic and diabetic subjects. For those individuals choosing to have a large number of small meals each day, it is relevant to emphasize that no untoward effects of increased meal frequency on lipids or lipoproteins have been demonstrated.


Efficacy of the Feliway® Classic Diffuser in reducing undesirable scratching in cats: A randomised, triple-blind, placebo-controlled study.
Scratching the environment is a natural behaviour that cats use for communication and physical maintenance purposes, however when it is carried out on household furniture it is considered unacceptable for some owners and even grounds for relinquishment of cats. The objective of this study was to investigate the efficacy of FELIWAY® Classic Diffuser in reducing undesirable scratching (scratching vertical surfaces indoors other than the scratching post) in cats. A 28 day, randomised, triple-blind, placebo-controlled study with a total of 1060 caregiver-cat dyads was conducted. The study contained two groups: the Pheromone Group consisted of caregivers who were given a pheromone diffuser (n = 546) and the Placebo Group consisted of caregivers who were given a placebo diffuser (n = 514). A questionnaire with three subsections was distributed online. The first section, completed by the respondents at day 0, inquired about the cats' daily routines, social and physical environments, behaviour, temperament, and emotional states. The second section filled on day 0, 7, 14, and 28, assessed the Frequency and the Intensity of the undesirable scratching problem and the effectiveness of the product. The last section, filled on the 28th day of the product application, related to the caregivers' opinions about the product and overall outcome. After 28 days the scratching Frequency reduced for 83.5% of the cats in the Pheromone Group and 68.5% for the Placebo Group (p<0.0001). The Intensity was significantly different between treatment groups at D7 (p = 0.0170), at D14 (p = 0.0189) and at D28 (p<0.001). The reduction of the Global Index Score, which was calculated by multiplying the Intensity with the Frequency, was significantly higher for the Pheromone Group (p<0.001). This study provides direct evidence that the use of FELIWAY® Classic diffuser significantly reduces the Frequency, Intensity and the Global Index Score of undesirable scratching.


[The prognostic significance of the therapeutic working alliance from the perspective of the patient and therapist].
In general, the prognostic relevance of a working alliance for both the course and the outcome of psychotherapy is no longer a matter of dispute. Since a working alliance is conceived as an interactional variable, the results must be interpreted on the basis of several important dimensions: the perspective of the investigator and the time structure during the course of therapy. Using the data available from the Berlin Psychotherapy Study (Rudolf 1991), we investigated for the 238 patients (inpatients and outpatients who received psychoanalytically oriented therapy in the study) the prognostic relevance of diagnostic and therapy-related working alliance variables for the various outcomes investigated. A complex correlation-statistical method (latent-trait-model) was used to consider the investigator perspective with regard to the working alliance and the outcome as well as the time structure and the diagnostic variables. Our results emphasize the relevance of the therapist's perspective beginning with the diagnostic indication, the working alliance and finally the outcome. The patient's perspective, however, seems to be less relevant. The results are presented and discussed in relation to the relevant literature. One result we have found as a further important dimension is that the kind of therapy carried out must be taken into consideration. This implies that as in our study for all phases of the investigation therapy specific instruments must be applied. In this regard our results also contribute to the validation of the instrument used to measure the working alliance TAB.


Elucidating the cell penetrating properties of self-assembling β-peptides.
Self-assembling lipopeptide hydrogels have been widely developed for the delivery of therapeutics due to their rapid gelation, injectability, and highly controlled physicochemical properties. Lipopeptides are also known for their membrane-associating and cell penetrating properties, which may impact on their application in cell-encapsulation. Self-assembling lipidated-β3-peptide materials developed in our laboratory have previously been used in cell culture as 2D substrates, thus as a continuation of this work we aimed to encapsulate cells in 3D by forming a hydrogel. We therefore assessed the self-assembling lipidated-β3-peptides for cell-penetrating properties in mesenchymal stems cells (MSC) using fluorescence microscopy and membrane association with surface plasmon resonance spectroscopy (SPR). The results demonstrated that lipidated β3-peptides penetrate the MSC plasma membrane and localise to the mitochondrial network. While self-assembling lipopeptide hydrogels have shown tremendous potential for delivery of therapeutics, further optimisation may be required to minimise the membrane uptake of the lipidated-β3-peptides for cell encapsulation applications.


Metal-Ion-Induced Switch of Liquid-Crystalline Orientation of Metallomacrocycles.
A new series of shape-persistent imine-bridged macrocycles were synthesized based on dynamic covalent chemistry. The macrocycles had an alternating sequence of dibenzothiophene and N,N'-bis(salicylidene)-ethylenediamine (salen) tethering branched alkyl chains. The macrocycles and tetranuclear metallomacrocycles bearing long and branched alkyl chains exhibited thermotropic columnar liquid-crystalline phases over a wide temperature range and the metallomacrocycles greatly depended on the characteristics of the coordinated metal ions. The metal-free macrocycle showed a liquid-crystalline phase with a lamellar structure and poor birefringence. In sharp contrast, the macrocyclic Ni complex showed a columnar oblique liquid-crystalline phase, whereas the Pd and Cu complexes showed columnar liquid-crystalline phases with a lamellar structure. The macroscopic organization and thermal properties of the corresponding liquid-crystalline metallomacrocycles were significantly dependent on the subtle structural differences among the planar macrocycles, which were revealed by single-crystal X-ray crystallographic analysis of the macrocycles with shorter alkyl chains.


The elderly liver transplant recipients: anxiety, depression, fatigue and life satisfaction.
Introduction Older patients are neglected in clinical trials and are likely to be excluded from liver transplantation (LT). The aim of this study was to assess fatigue, anxiety, depression, and health-related quality of life (HRQoL) in elderly LT recipients. Methods Questionnaires were mailed to patients who underwent LT between 1993 and 2013. Three groups were created: patients ≥ 70, 60 - 69, and < 60 years old. Mental-health status, life satisfaction, and fatigue were assessed using, respectively, the Hospital Anxiety and Depression Scale (HADS), Questions on Life Satisfaction (FLZ-M), and the Multidimensional Fatigue Inventory (MFI-20). Results In total, 276 eligible questionnaires (40.1 %) were received out of 689 patients with a history of LT. No age-related differences were found with regard to anxiety or depression in the study sample. Patients ≥ 70 years old had significantly better life satisfaction in regards to income (p = 0.003) and work (p = 0.005) compared to patients < 60 years. The overall fatigue scores were the highest in patients < 60 years (52.7, SD = 15.8) and ≥ 70 years (52.7, SD = 17.7) compared to patients 60 - 69 years old (48.2, SD = 17.3, p = 0.037). Discussion Advanced age alone should not be considered a contraindication for LT due to potentially poor quality of life outcomes.


T-cell responses against tuberculin and sensitin in children with tuberculosis and non-tuberculosis mycobacterial lymphadenopathy.
Multi-colour flow cytometry was applied to determine T-cell-specific interferon-gamma, interleukin-2 and tumour necrosis factor-alpha expression in children with tuberculosis and non-tuberculosis mycobacterial lymphadenopathy (NTM-L). In vitro stimulation of peripheral blood mononuclear cells with purified protein derivative from Mycobacterium tuberculosis (tuberculin) and M. avium (sensitin) revealed differential recognition of tuberculin and sensitin in both study groups. Ratios of tuberculin-specific and sensitin-specific T-cell proportions in individual patients discriminated between children with tuberculosis or NTM-L. These findings have the potential to improve the differential diagnosis of mycobacterial infections.


Report of two rare manifestations of abdominal tuberculosis mimicking neoplasia.
Abdominal tuberculosis (TB) can affect any organ of the gastrointestinal tract, and as a result of its unspecific symptoms, it may even mimic neoplasia. Rare manifestations are difficult to detect even for the trained eye and require clinical suspicion. We report rare cases of a mechanical ileus due to peritoneal TB in a 41-year-old man and an isolated peripancreatic infection in a 54-year-old woman. While in one patient, suspected malignancy led to diagnostic laparoscopy, it led to a total pancreatectomy with splenectomy in the other case. However, both times histology ruled out malignancy and showed unexpected similarities with TB. The patients responded well to medical treatment, although one patient is struggling with pancreatogenic diabetes.


Therapeutic feeding at a rural hospital in Zimbabwe.
The purpose of this audit was to review treatment outcomes of participants in the Cooperazione e sviluppo/Cooperation and Development (CESVI), Therapeutic Feeding Programme (TFP) (i.e., death vs cure vs absconded) and to make recommendations for improving this and other similar programmes. This study was a retrospective chart review. The charts of all patients admitted to the TFP from 1 January 2005 to 31 December 2005 were analyzed. The Salvation Army Howard Hospital is a district hospital in rural Zimbabwe. The hospital provides both inpatient and outpatient paediatric care. 132 consecutive children were enrolled in the TFP in 2005. The objectives of the TFP included identification of children with severe malnutrition; treating complications associated with severe malnutrition and prescribing appropriate dietary treatment. The main outcome of interest was whether TFP participants died, were cured, or absconded. We assessed factors that may be associated with these outcomes such as age, gender, comorbidities and length of stay. Female children and children with marasmus were more likely to abscond from the programme than male children and children with kwashiorkor (p = 0.041, 0.039 respectively). The majority of children who died while in the programme did so within the first week of their admission. The majority of children who were cured while in the programme achieved this goal after two weeks of hospitalization (p < 0.0001). Given the contextual factors in rural African settings that could potentially impede the healthy growth and development of children, this review has produced programmatic recommendations and suggestions for future research directions.


The Direction of response selectivity between conspecific and heterospecific auditory stimuli varies with response metric.
Species recognition is an essential behavioral outcome of social discrimination, flocking, mobbing, mating, and/or parental care. In songbirds, auditory species recognition cues are processed through specialized forebrain circuits dedicated to acoustic discrimination. Here we addressed the direction of behavioral and neural metrics of zebra finches' (Taeniopygia guttata) responses to acoustic cues of unfamiliar conspecifics vs. heterospecifics. Behaviorally, vocal response rates were greater for conspecific male zebra finch songs over heterospecific Pin-tailed Whydah (Vidua macroura) songs, which paralleled greater multiunit spike rates in the auditory forebrain in response to the same type of conspecific over heterospecific auditory stimuli. In contrast, forebrain activation levels were reversed to species-specific song playbacks during two functional magnetic resonance imaging experiments: we detected consistently greater responses to whydah songs over finch songs and did so independently of whether subjects had been co-housed or not with heterospecifics. These results imply that the directionality of behavioral and neural response selectivity metrics are not always consistent and appear to be experience-independent in this set of stimulus-and-subject experimental paradigms.