A Cost-Minimisation Analysis Comparing Sublingual Immunotherapy to Subcutaneous Immunotherapy for the Treatment of House Dust Mite Allergy in a Swedish Setting.
In Sweden, approximately 6% of children and 10% of adults suffer from house dust mite (HDM) allergy with symptoms of allergic rhinitis and allergic asthma. Treatment is aimed at reducing HDM exposure and to control the symptoms of allergic rhinitis and allergic asthma by symptom-relieving pharmacotherapy. This pharmacotherapy is often effective, but some patients remain inadequately controlled. For these patients, allergy immunotherapy (AIT, subcutaneous or sublingual) with repeated administration of HDM allergen should be considered. The objective of this study was to compare the costs for sublingual AIT (SLIT; SQ® SLIT-tablet) to the costs for subcutaneous AIT (SCIT; SQ® SCIT) for the treatment of HDM allergy in a cost-minimisation analysis (CMA). The CMA included resources (and costs) for treatment, healthcare visits, travelling and lost productivity. Resource use based on Swedish clinical treatment practice and costs were obtained from medical price lists. Analyses were conducted from the societal, as well as healthcare perspective, by use of a time horizon of 3 years. The results show that SQ® SLIT-tablet is a cost-saving treatment as compared to SQ® SCIT for the treatment of HDM allergy (€6800 over 3 years). The results are mainly driven by the cost of healthcare visits and the frequency of SCIT administrations. In conclusion, cost-savings of €6800 over 3 years are expected from treating HDM allergy with SQ® SLIT-tablet as compared to SQ® SCIT, including costs for treatment, healthcare visits, travelling and lost productivity. The reduced number of healthcare visits compensates for higher medication costs.


Dissemination of well water arsenic results to homeowners in Central Maine: influences on mitigation behavior and continued risks for exposure.
Private wells in the United States are unregulated for drinking water standards and are the homeowner's responsibility to test and treat. Testing for water quality parameters such as arsenic (As) is a crucial first step for homeowners to take protective actions. This study seeks to identify key behavioral factors influencing homeowners' decisions to take action after receiving well As test results. A January 2013 survey of central Maine households (n=386, 73% response) who were notified 3-7 years earlier that their well water contained As above 10 μg/L found that 43% of households report installing As treatment systems. Another 30% report taking other mitigation actions such as drinking bottled water because of the As, but the remaining 27% of households did not act. Well water As level appears to be a motivation for mitigation: 31% of households with well water level between 10 and 50 μg/L did not act, compared to 11% of households with well water >50 μg/L. The belief that the untreated water is not safe to drink (risk) and that reducing drinking water As would increase home value (instrumental attitude) were identified as significant predictors of mitigating As. Mitigating As exposure is associated with less worry about the As level (affective attitude), possibly because those acting to reduce exposure feel less worried about As. Use of a treatment system specifically was significantly predicted by confidence that one can maintain a treatment system, even if there are additional costs (self-efficacy). An assessment of As treatment systems used by 68 of these households with well water As >10 μg/L followed up within August-November 2013 found that 15% of treatment units failed to produce water below As 10 μg/L, suggesting that there are continued risks for exposure even after the decision is made to treat.


Association of Imaging-Based Body Fat Distribution and Mammographic Density in the Multiethnic Cohort Adiposity Phenotype Study.
As the stronger association of obesity with postmenopausal breast cancer in Asian than white women may be due to body fat distribution, we examined the relation of adiposity measures with percent mammographic density (PMD), a strong predictor of breast cancer incidence. A total of 938 women from five ethnic groups (69.1 ± 2.7 years) in the Adiposity Phenotype Study (APS) underwent DXA and MRI imaging. PMD was assessed in routine mammograms using a computer-assisted method. Spearman correlation coefficients were computed and general linear models were applied to estimate regression coefficients (β) for PMD per 0.5 SD units of adiposity measures while adjusting for known confounders, including DXA total body fat. For 701 (75%) of the participants (69.1 ± 2.7 years), valid mammograms were obtained. Whereas total body fat, the trunk-to-periphery fat ratio (TPFR), visceral fat (VAT), and subcutaneous fat (SAT) were inversely correlated with PMD (P < 0.0001), the VAT/SAT ratio correlated positively (r spearman = 0.10; P = 0.01). In fully adjusted models, PMD remained inversely related to TPFR and SAT and disappeared for VAT, while it was strengthened for VAT/SAT (β = 0.51; P = 0.009). This relation was stronger in Japanese Americans than other ethnic groups. This is the first study to show an association of a high VAT/SAT ratio with greater PMD, a marker of breast cancer risk after taking into account total body fat. The results indicate a link between the propensity to accumulate VAT and the amount of fat in the breast (1-PMD), which may influence the relation of obesity with breast cancer incidence.


New experience with the paracardial right ventricular axial flow micropump impella elect 600.
Beating heart surgery is still challenging and could be made safer using assisted circulation. We evaluated clinical outcome following beating heart myocardial revascularisation using the impella elect system with intracardial left ventricular (LV) and paracardial right ventricular (RV) microaxial pumps in eight patients. Clinical course was uneventful. There were no device-related complications. The paracardial design of the RV-pump is a great advantage compared to the former intracardial design because it eliminates arrhythmia and LV hypovolemia. Support by microaxial pumps can make beating heart surgery safer and applicable for more complex cases.


Multiparametric approach to assess the disease severity and progression of cutaneous leishmaniasis infection.
The pathophysiology of Cutaneous Leishmaniasis (CL), an infection caused by Leishmania tropica (L. tropica) and Leishmania major (L. major) is primarily determined by inflammation-mediated immune cells. The immune response mainly depends on cells and molecules related to T-cells that influence susceptibility and disease development. Understanding the immunological mechanisms that cause tissue injury or lesion healing is critical for developing appropriate treatment strategies. In the present study, T-cells profile and cell-free mitochondrial DNA (CF mt-DNA) were investigated in CL patients infected with L. tropica (n = 34) and L. major (n = 2) and compared with non-infected healthy controls (n = 20). There was a significant (p<0.0001) difference between CD4+ T-cells among L. tropica and L. major CL-infected groups as compared to control while no significant difference (p = 0.8597) was found in the percentages of CD8+ T-cells. When L. tropica and L. major CL-infected individuals were compared to controls, the levels of IL-4 and expression of CF mt-DNA were significantly higher (p<0.0001). Higher levels of CF mt-DNA were detected in CL patients, irrespective of the infective Leishmania species. We proposed that the levels of CF mt-DNA and IL-4 in CL-infected individuals can be used to determine the disease progression. A better understanding of these biomarkers and evaluation of the immune responses in CL patients might benefit the development of vaccines and immunotherapies.


Microglia activation contributes to quinolinic acid-induced neuronal excitotoxicity through TNF-α.
It has been reported that activation of NF-κB is involved in excitotoxicity; however, it is not fully understood how NF-κB contributes to excitotoxicity. The aim of this study is to investigate if NF-κB contributes to quinolinic acid (QA)-mediated excitotoxicity through activation of microglia. In the cultured primary cortical neurons and microglia BV-2 cells, the effects of QA on cell survival, NF-κB expression and cytokines production were investigated. The effects of BV-2-conditioned medium (BCM) on primary cortical neurons were examined. The effects of pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-κB, and minocycline (MC), an inhibitor of microglia activation, on QA-induced excitotoxicity were assessed. QA-induced NF-κB activation and TNF-α secretion, and the roles of TNF-α in excitotoxicity were studied. QA at the concentration below 1 mM had no apparent toxic effects on cultured primary neurons or BV-2 cells. However, addition of QA-primed BCM to primary neurons did aggravate QA-induced excitotoxicity. The exacerbation of QA-induced excitotoxicity by BCM was partially ameliorated by inhibiting NF-κB and microglia activation. QA induced activation of NF-κB and upregulation of TNF-α in BV-2 cells. Addition of recombinant TNF-α mimicked QA-induced excitotoxic effects on neurons, and neutralizing TNF-α with specific antibodies partially abolished exacerbation of QA-induced excitotoxicity by BCM. These studies suggested that QA activated microglia and upregulated TNF-α through NF-κB pathway in microglia. The microglia-mediated inflammatory pathway contributed, at least in part, to QA-induced excitotoxicity.


IKKβ acts as a tumor suppressor in cancer-associated fibroblasts during intestinal tumorigenesis.
Cancer-associated fibroblasts (CAFs) comprise one of the most important cell types in the tumor microenvironment. A proinflammatory NF-κB gene signature in CAFs has been suggested to promote tumorigenesis in models of pancreatic and mammary skin cancer. Using an autochthonous model of colitis-associated cancer (CAC) and sporadic cancer, we now provide evidence for a tumor-suppressive function of IKKβ/NF-κB in CAFs. Fibroblast-restricted deletion of Ikkβ stimulates intestinal epithelial cell proliferation, suppresses tumor cell death, enhances accumulation of CD4(+)Foxp3(+) regulatory T cells, and induces angiogenesis, ultimately promoting colonic tumor growth. In Ikkβ-deficient fibroblasts, transcription of negative regulators of TGFβ signaling, including Smad7 and Smurf1, is impaired, causing up-regulation of a TGFβ gene signature and elevated hepatocyte growth factor (HGF) secretion. Overexpression of Smad7 in Ikkβ-deficient fibroblasts prevents HGF secretion, and pharmacological inhibition of Met during the CAC model confirms that enhanced tumor promotion is dependent on HGF-Met signaling in mucosa of Ikkβ-mutant animals. Collectively, these results highlight an unexpected tumor suppressive function of IKKβ/NF-κB in CAFs linked to HGF release and raise potential concerns about the use of IKK inhibitors in colorectal cancer patients.


Abdominal wall abscess associated with perforated jejunal diverticulitis: report of a case.
We report a case of abdominal wall abscess caused by diverticulitis of the jejunum penetrating through the abdominal wall. A 53-year-old Japanese woman visited a local hospital complaining of abdominal pain and a mass in the left lower abdomen. An abdominal computed tomography scan showed a tumor with isodensity in the left lower abdominal wall. Magnetic resonance imaging showed a mass in the abdominal wall with isointensity in the T1-intensified image and high intensity in the T2-intensified images. The mass was heterogeneous inside and protruded partially toward the intraperitoneal cavity. Ultrasound examination showed a heteroechoic mass extending into the intraperitoneal cavity. Laparotomy revealed a tumor in the abdominal wall with a fistulous tract extending to the jejunum. We resected the abdominal wall tumor with partial resection of the small intestine. The resected specimen contained a tumor with a fistulous tract passing through the abdominal wall. Histological examination revealed remarkable infiltration of neutrophils and a bacterial mass in the abdominal wall tumor, with a fistulous tract connected to the area adjacent to the mesenteric border of the jejunum. These findings suggested that diverticulitis of the jejunum had penetrated through the abdominal wall, leading to the formation of an abscess. We report this case to highlight the need for complete gastrointestinal evaluation with gastrointestinal barium studies and imaging analysis to examine extension of intra-abdominal lesions in patients with an unexplained abdominal wall abscess.


Reassessment of verbal and visual analog ratings in analgesic studies.
The relative performance of three analgesic rating scales--visual pain analog, verbal pain intensity, and verbal pain relief--was assessed in clinical trials with 1,497 patients and a variety of pain models. The scales correlated strongly with one another, with inconsistent and generally minimal differences in sensitivity. Overall, the verbal relief scale tended to be slightly more sensitive than the pain analog rating, which in turn showed a small advantage over the verbal pain intensity assessment. When the scores derived from the categorized ratings 1 hour after drug dosing (generally the time of peak effect) were analyzed, there was little difference whether a parametric or nonparametric approach was taken. When the cumulative measures of overall effect over 6 hours were considered, however, the nonparametric approach was decidedly more powerful. There was a similar pattern when the analog scores were analyzed. This unanticipated finding appears to be due to the cumulative measures (from all three scales) being more skewed toward the lower end of their respective ranges than are the 1-hour scores. A composite efficacy variable was defined, incorporating data from the three primary scales; this measure was found to be generally comparable in sensitivity to the individual scales and may be useful as a global summary of response. While our investigation provides evidence that any of the ratings considered will accurately reflect analgesic response, the verbal relief scale was the most sensitive and might be the best choice if a single measure is desired.


Features of cancer in teenagers and young adults in primary care: a population-based nested case-control study.
Teenagers and young adults (TYA, 15-24 years) diagnosed with cancer report repeated visits to primary care before referral. We investigated associations of symptoms and consultation frequency in primary care with TYA cancers. Population-based, case-control study was carried out using data from the Clinical Practice Research Datalink (CPRD). A total of 1064 TYA diagnosed with cancer were matched to 13,206 controls. Symptoms independently associated with specific cancers were identified. Likelihood ratios (LRs) and positive predictive values (PPVs) were calculated. In the 3 months before diagnosis, 397 (42.9%) cases consulted > or =4 times vs 593(11.5%) controls (odds ratio (OR): 12.1; 95% CI: 9.7, 15.1), yielding a PPV for any cancer of 0.018%. The LR of lymphoma with a head/neck mass was 434 (95% CI: 60, 3158), with a PPV of 0.5%. Corresponding figures in other cancers included - LR of leukaemia with lymphadenopathy (any site): 29 (95% CI: 8, 112), PPV 0.015%; LR of CNS tumour with seizure: 56 (95% CI: 19, 163), PPV 0.024%; and LR of sarcoma with lump/mass/swelling: 79 (95% CI: 24, 264), PPV 0.042%. Teenagers and young adults with cancer consulted more frequently than controls in the 3 months before diagnosis. Primary care features of cancer match secondary care reports, but were of very low risk; nonetheless, some features increased the likelihood of cancer substantially and should be taken seriously when assessing TYA.


Canadian dietitians' approaches to counseling adult clients seeking weight-management advice.
This study describes Canadian dietitians' approaches to counseling adults seeking weight-management advice. Fifteen focus groups were conducted at seven sites across Canada. The participants, most of whom worked in clinical or private practice, discussed their approach to specific weight-management counseling scenarios, including women clients with and without associated risk factors (impaired glucose tolerance, hypertension, family history of cardiovascular disease) and long histories of dieting. Results indicate that participants used a lifestyle approach for weight-management counseling, where the main goal was improved client health through healthful eating and increased physical activity. In contrast to clients' perceived weight loss goals, participants rarely included weight loss as a goal for clients with no additional chronic disease risk factors. For clients with risk factors, some participants advocated moderate weight loss, while others aimed for health at any size. Participants also discussed the importance of clients' psychological well-being, particularly in relation to feelings about food and body image. Individualized approaches to setting goals, gathering information, and giving advice/educating were identified as key counseling strategies. Further research to evaluate the effectiveness of dietitians' weight-management approaches and additional counseling training for dietitians will enhance practitioners' skills and confidence in this area.


A comparative study of localization of heat shock protein 27 and heat shock protein 72 in the developmental and degenerative intervertebral discs.
The lumbar intervertebral discs of 135 subjects after autopsy were immunostained with antihuman heat shock protein 27 (HSP27) monoclonal antibody and antihuman heat shock protein 72 (HSP72) polyclonal antibody. To present the data on metabolic changes that occurred in the chondrocytes of intervertebral discs during development and aging. Heat shock proteins have been implicated in the progressive degeneration of articular cartilage in joint disease, such as rheumatoid arthritis and osteoarthritis. However, the role and expression of heat shock proteins in human intervertebral discs have received little study. One hundred thirty-five specimens of human intervertebral discs were stained with hematoxylin and eosin, alcian blue, and Masson's trichrome and were immunostained with HSP27 and HSP72 by an indirect immunoperoxidase method. The relative amounts of HSP27 and HSP72 deposition were graded according to a semiquantitative scoring system. Heat shock protein 72 accumulated in the cytoplasm of the chondrocytes of both endplate cartilage and nucleus pulposus during gestation and thereafter decreased with aging (age, </=60 years), and HSP72 immunoreactivity increased in the chondrocytes of degenerative discs. In addition, HSP72 was located in the nuclei of certain chondrocytes of the degenerated nucleus pulposus and anulus fibrosus, was highly expressed in the chondrocytes of endplate cartilage during gestation and childhood, and thereafter decreased with aging. Furthermore, with the progressive degeneration of the endplate cartilage, HSP27 immunoreactivity increased. The degree of HSP27 immunoreactivity did not change significantly according to age in either the nucleus pulposus or the anulus fibrosus. Heat shock protein 27 and HSP72 are thus considered to be useful molecular indicators for degenerative change in intervertebral discs. Both HSP27 and HSP72 are presumed to play a role in cell protection from stress that is induced by mechanical and biologic factors causing intervertebral disc degeneration.


Diffuse Neuroendocrine Hyperplasia with Obliterative Bronchiolitis and Usual Interstitial Pneumonia: An Unusual "Headcheese Pattern" with Nodules.
A 74-year-old non-smoker female presented to our attention with a history of dyspnea and cough. CT scan revealed multiple areas of patchy ground glass attenuation associated to a diffuse mosaic oligoemia. Scattered bilateral subcentimetric pulmonary nodules were also present. Patient underwent a surgical lung biopsy. Specimens showed features of diffuse neuroendocrine hyperplasia, microhoneycombing, fibroblast foci. A final diagnosis of diffuse neuroendocrine hyperplasia with obliterative bronchiolitis and UIP was rendered.


Chaotic-map based authenticated security framework with privacy preservation for remote point-of-care.
The challenge of COVID-19 has become more prevalent across the world. It is highly demanding an intelligent strategy to outline the precaution measures until the clinical trials find a successful vaccine. With technological advancement, Wireless Multimedia Sensor Networks (WMSNs) has extended its significant role in the development of remote medical point-of-care (RM-PoC). WMSN is generally located on a communication device to sense the vital signaling information that may periodically be transmitted to remote intelligent pouch This modern remote system finds a suitable professional system to inspect the environment condition remotely in order to facilitate the intelligent process. In the past, the RM-PoC has gained more attention for the exploitation of real-time monitoring, treatment follow-up, and action report generation. Even though it has additional advantages in comparison with conventional systems, issues such as security and privacy are seriously considered to protect the modern system information over insecure public networks. Therefore, this study presents a novel Single User Sign-In (SUSI) Mechanism that makes certain of privacy preservation to ensure better protection of multimedia data. It can be achieved over the negotiation of a shared session-key to perform encryption or decryption of sensitive data during the authentication phase. To comply with key agreement properties such as appropriate mutual authentication and secure session key-agreement, a proposed system design is incorporated into the chaotic-map. The above assumption claims that it can not only achieve better security efficiencies but also can moderate the computation, communication, and storage cost of some intelligent systems as compared to elliptic-curve cryptography or RSA. Importantly, in order to offer untraceability and user anonymity, the RM-PoC acquires dynamic identities from proposed SUSI. Moreover, the security efficiencies of proposed SUSI are demonstrated using informal and formal analysis of the real-or-random (RoR) model. Lastly, a simulation study using NS3 is extensively conducted to analyze the communication metrics such as transmission delay, throughput rate, and packet delivery ratio that demonstrates the significance of the proposed SUSI scheme.


Adolescents' attitudes toward peers who wear visible hearing aids.
The purpose of this study was to determine how adolescents are likely to react to peers who wear visible hearing aids. Forty high school juniors and seniors rated a photograph of a male peer on an 81-scale semantic differential. One-half rated a copy of the photograph in which a hearing aid was visible and the others rated a copy in which one was not visible. Analyses of the ratings suggest that adolescents are likely to react negatively to peers who wear visible hearing aids. Clinical implications are discussed.


Isolation of nucleoli from Ehrlich ascites tumor cells and dynamics of nascent RNA within isolated nucleoli.
Here we describe a new, rapid method for isolating nucleoli from Ehrlich tumor cells that preserves their morphological integrity and high transcriptional activity. Until now, methods for isolation of nucleoli were generally assumed to empty one of their three main compartments, the fibrillar center, of its contents. This new method consists of sonicating cells in an isotonic medium containing MgSO(4), spermidine, and spermine, followed by separation of nucleoli through a Percoll density gradient. Using the nonisotopic approach of labelling with BrUTP, we have further investigated the dynamics of nascent ribosomal RNAs (rRNAs) within morphologically intact isolated nucleoli at the electron microscope level. We show that ribosomal transcripts are elongated in the cortex of the fibrillar center and then enter the surrounding dense fibrillar component.


In situ hybridization shows distinct patterns of mucin gene expression in normal, benign, and malignant pancreas tissues.
Northern blotting and immunohistochemistry have shown cell-specific patterns of mucin gene expression in the pancreas and alterations associated with neoplastic transformation. The aim of this study was to determine the presence of mucin transcripts at the single cell level in tissue samples from normal pancreas and benign and malignant pancreatic proliferative lesions. In situ hybridization with 35S-labeled oligonucleotides was performed on sections of paraffin-embedded tissues. Acinar cells express only MUC1. Normal pancreatic ducts show homogeneous expression of MUC1 and MUC5B and heterogenous expression of MUC3. MUC2, MUC4, and MUC5AC are generally undetectable in all cells of normal pancreas tissue. Pancreas cancers generally express MUC1, MUC3, MUC4, MUC5B and MUC5AC. Obstructive chronic pancreatitis adjacent to pancreas cancers shows the same pattern of mucin gene expression as normal ducts. In areas of papillary hyperplasia, altered expression of MUC3, MUC5B, and MUC5AC is observed. In situ hybridization has confirmed that neoplastic transformation of the exocrine pancreas is accompanied by changes in mucin gene expression. Although this type of change is not restricted to cancer cells, the findings of this study suggest that analysis of mucin gene expression may be of value in the differential diagnosis of pancreatic lesions.


Long-term health-related quality of life after complex and/or complicated esophageal atresia in adults and children registered in a German patient support group.
Health-related quality of life (HRQoL) after esophageal atresia (EA) repair is postulated to be good. However, little is known about the long-term results after repair of complex and/or complicated EA regarding HRQoL. We investigated long-term HRQoL after delayed anastomosis, esophageal replacement, major revisions, or multiple dilatations in patients registered in a support group. Patients registered in the German patient support group database (KEKS) were enrolled and allocated to subgroups according to surgical treatment and age. HRQoL was evaluated using validated questionnaires (GIQLI, WHO-5, KIDSCREEN27). Complete follow-up (mean 14.5 ± 9.8 years) was available for 90/92 patients. Patients were allocated to subgroups delayed anastomosis (n=28), esophageal replacement (n=27), major revisions (n=15), and multiple dilatations (n=20). Adult patients presented with impaired well-being according to WHO-score and gastrointestinal function (GIQLI). In contrast, HRQoL of children was comparable to controls in most KIDSCREEN27-dimensions. Delayed anastomosis was associated with most-favourable HRQoL. Regarding physical well-being, these children scored significantly better than controls [64.01 ± 10.40 vs. 52.36 ± 8.73;p=0.0011], children after replacement [51.40 ± 5.70;p=0.008], revisions [52.04 ± 6.97;p=0.026], and multiple dilatations [50.22 ± 9.67,p=0.04]. HRQoL after complex and/or complicated EA is excellent in children registered in a patient support group. In adults, disease-specific symptoms negatively affect HRQoL. Our data indicate that saving the esophagus may achieve the best HRQoL.


The opioid octapeptide Met5-enkephalin-Arg6-Gly7-Leu8: characterization and distribution in rat spinal cord.
The regional quantitation, immunohistochemical localization and molecular heterogeneity of Met5-enkephalin-Arg6-Gly7-Leu8 were examined in rat spinal cord with a specific radioimmunoassay. A rostrocaudal gradient in Met5-enkephalin-Arg6-Gly7-Leu8 content was observed; the highest levels occurred in sacral cord. Dorsal cord content was higher than that of ventral cord at all spinal segments. Immunohistochemical staining supported and refined the latter observation: a dense network of perikarya and fibers was found in Laminae I and II of the dorsal horn. Cell bodies were frequently observed in lamina IV. Additional terminals were seen around the central canal and in the ventral gray matter, often outlining perikarya of motor neurons. Total Met5-enkephalin-Arg6-Gly7-Leu8 immunoreactivity could be fractionated into two main components using gel filtration chromatography. Nearly half of the total immuno-reactivity eluted as a high molecular weight peptide; the other half which co-eluted with Met5-enkephalin-Arg6-Gly7-Leu8 was further identified to be authentic Met5-enkephalin-Arg6-Gly7-Leu8 on reverse phase high pressure liquid chromatography. The present data, in conjunction with our previous study of Met5-enkephalin and Met5-enkephalin-Arg6-Phe7 indicates that all opioid peptides derived from preproenkephalin A are present in spinal cord and most likely are stored in the same neurons. Immunohistochemical localization of Met5-enkephalin-Arg6-Gly7-Leu8 in dorsal and ventral cord suggest a role for this peptide in both sensory and motor integration.


Comparison of controlled ovarian stimulation with human menopausal gonadotropin or recombinant follicle-stimulating hormone.
To carefully examine the features of controlled ovarian stimulation performed with recombinant FSH-alpha or hMG. Controlled, prospective, randomized comparison of fixed gonadotropin regimens. Academic research institution. Fifty infertile patients who were candidates for IUI. Patients were randomized to receive a fixed regimen of recombinant FSH-alpha (150 IU/day, 25 patients) or hMG (150 IU/day, 25 patients), after GnRH-agonist suppression (long regimen). Daily measurements of serum LH, immunoreactive FSH, hCG, E(2), P, and T. Transvaginal pelvic ultrasound every 2 days. Pregnancy and abortion rates. Cost of medications. Two recombinant FSH-alpha-treated patients did not respond. Despite matched daily FSH dose, duration of treatment (hMG 10.8 +/- 0.4 vs. recombinant FSH-alpha 12.4 +/- 0.5 days), gonadotropin dose (21.7 +/- 0.8 vs. 25.3 +/- 1.3 ampoules), gonadotropin cost (288 +/- 10 vs. 1,299 +/- 66 /cycle), serum P levels, and small preovulatory follicle number were significantly lower, and LH, hCG, immunoreactive FSH levels, and larger follicles on day 8 were significantly higher in hMG-treated patients. The pregnancy, abortion, and twin pregnancy rates did not differ. The hMG administration was associated with: [1]. increased serum LH activity and immunoreactive FSH levels during treatment; [2]. reduced signs of premature luteinization; [3]. differential modulation of folliculogenesis; [4]. lower treatment duration, gonadotropin dose, and cost; and [5]. clinical outcome comparable to recombinant FSH-alpha.


Final checkup of neoplastic DNA replication: evidence for failure in decision-making at the mitotic cell cycle checkpoint G(1)/S.
Processing of epigenomic transcriptional information by cell cycle phase G(1) and decision-making at checkpoint G(1)/S are the final organizational steps preceding gene replication in transcriptional reorientation programs (i.e., switches from proliferation to cycle arrest and neoplastic transformation). Further analyses of cycle progression will open up new approaches in antineoplastic therapy. The following bibliographic databases were consulted: Central Medical Library Cologne, PubMed (English), the last search was done on April 23,2008 and key words searched were: cell cycle, cell memory, DNA methylation, embryonal/neoplastic stem cells, enzyme-modulated chromatin, G(1)-G(1)/S checkpoint, genomic/epigenomics, genomic viral DNA, histones, telomere/telomerases, transcription factors, neoplastic transformation, senescence. Gene transcription and epigenomic surveillance form a functional entity. In proliferation programs, transcriptional information is mediated by chromatin and DNA methylation, analyzed and processed in G(1) phase, and converged on the parental checkpoint G(1)/S for final decision-making on DNA replication. Genomic reorientation appears to be associated with transcriptional instability, which normally is corrected, possibly during the G(2)/M phase, to new levels of epigenomic equilibria. We speculate that daughter stem cells inherit persistent neoplasm-specific transcriptional instabilities through failure of the parental G(1)/S checkpoint. Foreign, silenced, potentially oncogenic DNA sequences, i.e. regular components of the human genome such as endogenous retroviruses, could conceivably be activated for expression in neoplastic transformation by epigenomic histone deacetylase/acetyl transferase/histone methyltransferase-mixed lineage leukemia deregulations. Failure of cell cycle G(1)/S decision-making for DNA replication is the final and possibly a major cause in neoplastic transformation. Therefore, further analysis of the dynamics of G(1)-G(1)/Sphases could provide new opportunities for therapeutic strategies.


Opposing roles for the nucleus accumbens core and shell in cue-induced reinstatement of food-seeking behavior.
Reinstatement of previously extinguished instrumental responding for drug-related cues has been used as an animal model for relapse of drug abuse, and is differentially affected by inactivation of the core and shell subregions of the nucleus accumbens (NAc). To compare the roles of these subregions in reinstatement induced by cues associated with natural and drug rewards, the present study assessed the effects of inactivation of the NAc core and shell on cue-induced reinstatement of food-seeking behavior. Rats acquired a lever pressing response for food reward paired with a light/tone conditioned stimulus (CS). They were then subjected to extinction, where both food and the CS were withheld. Reinstatement of responding was measured during response-contingent presentations of the CS. Following saline infusions into the NAc core or shell, rats displayed a significant increase in lever pressing during reinstatement sessions. Inactivation of the core, induced by infusion of GABA agonists muscimol and baclofen, attenuated responding for the CS, but did not affect pavlovian approach toward the food receptacle. In contrast, inactivation of the shell had the opposite effect, potentiating responding relative to vehicle treatments. These data suggest that the NAc core and shell play opposing, yet complementary roles in mediating the influence that food-associated conditioned stimuli exert over behavior. The core enables reward-related stimuli to bias the direction and vigor of instrumental responding. In contrast, the shell facilitates alterations in behavior in response to changes in the incentive value of conditioned stimuli. The fact that the NAc core appears to play a similar role in cue-induced reinstatement induced by both natural and drug rewards suggests that this region of the ventral striatum may be a final common pathway through which both drug- and food-associated stimuli may influence the direction and magnitude of ongoing behavior.


Evaluation of a genetic risk score computed using human chromosomal-scale length variation to predict breast cancer.
The ability to accurately predict whether a woman will develop breast cancer later in her life, should reduce the number of breast cancer deaths. Different predictive models exist for breast cancer based on family history, BRCA status, and SNP analysis. The best of these models has an accuracy (area under the receiver operating characteristic curve, AUC) of about 0.65. We have developed computational methods to characterize a genome by a small set of numbers that represent the length of segments of the chromosomes, called chromosomal-scale length variation (CSLV). We built machine learning models to differentiate between women who had breast cancer and women who did not based on their CSLV characterization. We applied this procedure to two different datasets: the UK Biobank (1534 women with breast cancer and 4391 women who did not) and the Cancer Genome Atlas (TCGA) 874 with breast cancer and 3381 without. We found a machine learning model that could predict breast cancer with an AUC of 0.836 95% CI (0.830.0.843) in the UK Biobank data. Using a similar approach with the TCGA data, we obtained a model with an AUC of 0.704 95% CI (0.702, 0.706). Variable importance analysis indicated that no single chromosomal region was responsible for significant fraction of the model results. In this retrospective study, chromosomal-scale length variation could effectively predict whether or not a woman enrolled in the UK Biobank study developed breast cancer.


Reuse of disposable medical devices in Canadian hospitals.
A survey of all Canadian hospitals was undertaken in 1986 to determine the extent of the reuse of disposable medical devices meant for "single use only." It was found that 41% of hospitals regularly reused disposable medical devices, and reuse was significantly higher in hospitals with more than 200 beds. Only 38% of hospitals that regularly reused had written procedures for reuse, and 32% indicated a mechanism for determining the number of times a device was reused. Cost analysis studies had been undertaken by only 29% of regular reusers, and items of respiratory therapy equipment were the most commonly reused devices.


Background and fingerprint characteristics of anthropogenic 236U and137Cs in soil and road dust samples collected from Beijing and Zhangjiakou, China.
236U has attracted more attention as an environmental tracer in recent years. However, in-depth study of 236U in terrestrial environments is still rare in China. Data on 236U and 137Cs concentrations in soil and road dust samples collected from Beijing and Zhangjiakou, China were obtained to demonstrate the background and distinct characteristics of anthropogenic 236U and 137Cs. 236U and 137Cs were detected in the range of (1.10-7.90) × 107 atoms g-1 and below the method limits of detection to 5.30 Bq kg-1. A clear characteristic was observed in road dust, where 236U concentrations increased with decreasing of sample particle size. Soil samples showed an irregular characteristic, but the highest 236U concentrations were observed in particle size fraction of <0.053 mm in both samples. This phenomenon was caused by U chemical properties, higher specific surface areas and organic compounds in fine particles. Anthropogenic radionuclides fingerprint characteristics in <0.053 mm samples were specially discussed. 236U/238U atom ratios were detected in the range of (0.627-3.38) × 10-8. A weak correlation between anthropogenic 236U and natural U isotopes were observed. The intermediate correlation between 236U and 137Cs indicated somewhat distinct migration behavior of these two radionuclides in soil after release to the environment. The released amount of 236U from global fallout during the period of atmospheric nuclear weapons testing was roughly estimated to be 1300 ± 448 kg. These results could be used as fingerprint information for anthropogenic 236U migration behavior and tracer application in environment.


[Justification of the indications for radio-frequency electrostimulation of the atria and the results of its use in paroxysmal supraventricular tachycardias].
Re-entry tachycardia was found in 182 patients of a total of 275 subjected to electrophysiological investigation of heart function; in 26 of those, a radio-frequency atrial electrostimulation system was implanted. Early postoperative complications were noted in 3 patients: subcutaneous hematoma in 2, and skin decubitus in 1. Long-term follow-up (as long as 7 years) confirmed the efficiency of atrial radio-frequency pacing.


Alterations in kynurenine precursor and product levels in schizophrenia and bipolar disorder.
Increased concentrations of kynurenine pathway metabolites have been reported by several groups for disorders involving psychosis, including schizophrenia and bipolar disorder. To identify components of the pathway that may be relevant as biomarkers or may underlie the etiology of psychosis, it is essential to characterize the extent of kynurenine pathway activation and to investigate known regulators of one of the key kynurenine-producing enzymes, tryptophan 2,3-dioxygenase (TDO2), previously shown in this laboratory to be increased commensurate with kynurenine in postmortem anterior cingulate brain tissue from individuals with schizophrenia. Using this same anterior cingulate sample set from individuals with schizophrenia, bipolar disorder, depression and controls (N=12-14 per group), we measured the precursor of kynurenine and two downstream products. The precursor, tryptophan, was significantly increased only in the schizophrenia group (1.54-fold the mean control value, p=0.02), and through substrate-induced activation, may be one cause of the increased kynurenine and kynurenine metabolites. This finding for tryptophan differs from some, but not all, previous reports and methodological reasons for the discrepancies are discussed. A product of kynurenine metabolism, 3-OH-anthranilic acid was also significantly increased only in the schizophrenia group (1.68-fold the mean control value, p=0.03). 3-OH-anthranilic acid is a reactive species with cytotoxic properties, although the threshold for such effects is not known for neurons. Analysis of major pre- and post-mortem variables showed that none were confounding for these between-group experimental comparisons. Nicotinamide, a pathway end product, did not differ between groups but was associated with cause of death (suicide) within the bipolar group (p=0.03).


How inhibitory cues can both constrain and promote cell migration.
Collective cell migration is a common feature in both embryogenesis and metastasis. By coupling studies of neural crest migration in vivo and in vitro with mathematical modeling, Szabó et al. (2016, J. Cell Biol., http://dx.doi.org/10.1083/jcb.201602083) demonstrate that the proteoglycan versican forms a physical boundary that constrains neural crest cells to discrete streams, in turn facilitating their migration.


BAP1 in cancer: epigenetic stability and genome integrity.
Mutations in BAP1 have been identified in a hereditary cancer predisposition syndrome and in sporadic tumours. Individuals carrying familiar BAP1 monoallelic mutations display hypersusceptibility to exposure-associated cancers, such as asbestos-driven mesothelioma, thus BAP1 status has been postulated to participate in gene-environment interaction. Intriguingly, BAP1 functions display also a high degree of tissue dependency, associated to a peculiar cancer spectrum and cell types of specific functions. Mechanistically, BAP1 functions as an ubiquitin carboxy-terminal hydrolase (UCH) and controls regulatory ubiquitination of histones as well as degradative ubiquitination of a range of protein substrates. In this article we provide an overview of the most relevant findings on BAP1, underpinning its tissue specific tumour suppressor function. We also discuss the importance of its epigenetic role versus the control of protein stability in the regulation of genomic integrity.


Glycosyl and polyalcoholic prodrugs of lonidamine.
Polyhydric alcohol derivatives of the anticancer agent lonidamine (LND) have been synthesized. The increased water solubility showed by prodrugs 4, 7, and 25 together with their logP values (2.19, 2.55, and 2.54, respectively) and chemical stability might be beneficial for prodrugs absorption after oral administration. Moreover, the new prodrugs undergo enzymatic hydrolysis in plasma and release LND demonstrating that they are promising candidates for in vivo investigations.


Integrating life-history and reproductive success data to examine potential relationships with organochlorine compounds for bottlenose dolphins (Tursiops truncatus) in Sarasota Bay, Florida.
Research initiated in 1970 has identified a long-term, year-round resident community of about 140 bottlenose dolphins (Tursiops truncatus) in Sarasota Bay, Florida, providing unparalleled opportunities to investigate relationships between organochlorine contaminant residues and life-history and reproductive parameters. Many individual dolphins are identifiable and of known age, sex, and maternal lineage (< or =4 generations). Observational monitoring provides data on dolphin spatial and temporal occurrence, births and fates of calves, and birth-order. Capture-release operations conducted for veterinary examinations provide biological data and samples for life-history and contaminant residue measurement. Organochlorine concentrations in blubber and blood (plasma) can be examined relative to age, sex, lipid content, and birth-order. Reproductive success is evaluated through tracking of individual female lifetime calving success. For the current study, 47 blubber samples collected during June 2000 and 2001 were analyzed for PCB concentrations of 22 congeners relative to life-history factors and reproductive success. Prior to sexual maturity, males and females exhibited similar concentrations of about 15-50 ppm. Classical patterns of accumulation with age were identified in males, but not in females. Subsequently, males accumulated higher concentrations of PCBs through their lives (>100 ppm), whereas females begin to depurate with their first calf, reaching a balance between contaminant intake and lactational loss (<15 ppm). In primiparous females, PCB concentrations in blubber and plasma and the rates of first-born calf mortality were both high. First-born calves had higher concentrations than subsequent calves of similar age (>25 vs.<25 ppm). Maternal burdens were lower early in lactation and increased as calves approached nutritional independence. Empirical data were generally consistent with a published theoretical risk assessment and supported the need for incorporation of threats from indirect anthropogenic impacts such as environmental pollutants into species management plans. Long-term observational monitoring and periodic biological sampling provide a powerful, non-lethal approach to understanding relationships between organochlorine residue concentrations in tissues and reproductive parameters for coastal dolphins.


The aqueous assembly preparation of OPs-AgNPs with phenols from olive mill wastewater and its mechanism on antimicrobial function study.
To valorise olive mill wastewater phenols (OPs) potentially applied in food preservation, a novel stable and regularly spherical OPs-AgNPs (Davg = 78 nm) were successfully assembled in aqueous solution under the optimized conditions (pH 8.0, 5 mM AgNO3, 35C and 30 min). The results of antimicrobial zone diameters indicated that 50 μg/mL of promising OPs-AgNPs presented excellent antimicrobial effects. Especially, the cell wall damages of E. coli ATCC 23,815 were caused when OPs-AgNPs concentration was exceeded its MIC (8.58 μg/mL). Also, a significant down-regulating of the Ca2+-ATPase activity in E. coli was revealed, and the intracellular Ca2+ concentrations were thus decreased from 12.5 to 1.35 µg/mL after a treatment for 3 h. The apoptosis level of E. coli was significantly increased more than the control (55.13% of OPs-AgNPs vs 9.90% of control). In sum, OPs exerts enhanced antimicrobial function via penetrating cell membrane and targeting Ca2+-ATPase after chelated with AgNPs.


Tuberculosis screening in immigrants from high-prevalence countries: interview first or chest radiograph first? A pro/con debate.
Immigration from high tuberculosis (TB) prevalence countries has a substantial impact on the epidemiology of TB in receiving countries with low TB incidence. Cross-border migration offers an ideal opportunity for active case finding that will result in a lower caseload in the host country and a reduced spread of disease to both the indigenous and migrant populations. Screening strategies can start 'offshore', thereby indirectly assisting and empowering public health systems in the source countries, or be performed at ports of entry with or without long-term engagement of 'onshore' facilities and systems to provide either preventive therapy or surveillance for reactivation of latent TB. The chest radiograph seems to be playing a key role in this process, but questions remain regarding when, where and in whom radiographs are best done for optimal yield and cost-effectiveness, and with what other tests they might best be combined to further increase the usefulness of transborder TB control.


Release of fibrinolytic activators from the cornea and conjunctiva.
The authors studied the release of fibrinolytic activators from in vitro cultures of human and animal cornea with the following main findings: (1) the epithelium is the main activator source; (2) the addition of tripeptide, salicylate, chloroquine and phorbolester to the culture medium increases the fibrinolytic activity of the cultures; (3) corticosteroids depress the fibrinolytic activity; (4) explants of human conjunctiva also release fibrinolytic activators. The pathophysiological role of this activator is unknown. Hypothetically, besides preventing fibrin deposition on the surface of the eye, this activator may also stimulate leucocyte migration, activate procollagenase, protect the endothelial pump, and regulate vascular permeability and angiogenesis in the cornea.


Collagen abnormalities in the spinal cord from patients with amyotrophic lateral sclerosis.
During the last 10 years, we have demonstrated morphological and biochemical abnormalities of skin extracellular matrices in amyotrophic lateral sclerosis (ALS). However, currently little is known concerning collagen of the spinal cord in ALS. We measured the amount of collagen and characterized collagen at light and electron microscopic levels in posterior funiculus, posterior half of lateral funiculus and anterior horn of cervical enlargement of the spinal cord obtained from ten patients with ALS, 11 patients with other neurologic diseases (control group A), and ten patients without neurologic ones (control group B). In posterior half of lateral funiculus and anterior horn, (1) by light microscopy, there was no significant difference in vessel wall area between ALS patients and control groups A and B; (2) ultrastructurally, collagen bundles were more fragmented and widely separated, and the fibrils were randomly oriented in the perivascular space of capillaries in ALS patients, which were not observed in any areas of control groups or in posterior funiculus of ALS patients; and (3) the collagen contents in ALS were significantly lower (P<0.001 and P<0.001, respectively) than those in control groups A and B. Fragmented and widely separated collagen bundles in the interstitial tissue surrounding capillaries and markedly decreased amount of collagen in posterior half of lateral funiculus and in anterior horn of ALS could be related to the degeneration of the upper and lower motor neurons in the spinal cord in ALS, that is, selective neuronal vulnerability in ALS.


An analysis of the permeability of a fenestra.
In this analysis of published data we evaluate the permeabilities of unit area of fenestral pathway to water and small solutes. These properties are then used to assess the functional significance of the fenestral diaphragm which, along with the glycocalyx and basement membrane, makes up the fenestral pathway. Endothelial hydraulic conductance and permeability to small lipophobic solutes increase with fenestral density in a variety of mammalian tissue. The increase in conductance per unit increment in fenestral area (Kfen) averages 0.38 micron X s-1 X mm Hg-1 (regression analysis). This value means that a single fenestra (diam 0.06 micron, area 0.003 micron2) has a greater conductance than 1 micron2 of continuous (skeletal muscle) endothelium. Similarly the diffusional permeability of unit fenestral area (Pfen) to B12 and inulin is high. But neither Kfen nor Pfen is as great as might be expected from the extreme thinness of the diaphragm (less than or equal to 5 nm). Pfen depends on diffusivity (D) and pathlength (delta chi): Pfen = D'/delta chi. D' depends on the fraction of the fenestral surface available for exchange and on restriction to diffusion. These relations were applied to test the view that the diaphragm, rather than the glycocalyx or basement membrane, is the major barrier to fluid and small solutes in the fenestral pathway. If this were turn, over 98 1/2% of the diaphragm's area would have to be totally impermeable in order to yield the observed values of Pfen--a result consequent upon the extreme thinness of the diaphragm. In this event there would be less than one equivalent pore (radius 5-11 nm) per diaphragm on average-which is incompatible with ultrastructural evidence. The resistance of a 5-nm-thick diaphragm containing one or more pores is not high enough to account for fenestral resistance. It is concluded that much thicker structures, such as the glycocalyx and/or basement membrane, and not the diaphragm, account for fenestral resistance to small-solute and water transport.


MESSENGER observations of the spatial distribution of planetary ions near Mercury.
Global measurements by MESSENGER of the fluxes of heavy ions at Mercury, particularly sodium (Na(+)) and oxygen (O(+)), exhibit distinct maxima in the northern magnetic-cusp region, indicating that polar regions are important sources of Mercury's ionized exosphere, presumably through solar-wind sputtering near the poles. The observed fluxes of helium (He(+)) are more evenly distributed, indicating a more uniform source such as that expected from evaporation from a helium-saturated surface. In some regions near Mercury, especially the nightside equatorial region, the Na(+) pressure can be a substantial fraction of the proton pressure.


Preliminary results of prognostic significance of proliferating cell nuclear antigen expression in advanced primary larynx carcinomas and lymph node metastases.
The aim of this study was to investigate the prognostic significance of proliferating cell nuclear antigen (PCNA) expression in laryngeal carcinoma in relation to clinicopathological features. Special emphasis was placed on examining the relationship of PCNA expression in the primary tumour and PCNA expression in corresponding lymph node metastases obtained from the same patients. The study included 60 patients with advanced larynx carcinoma who had received treatment and follow-up for at least 5 years. Sixty laryngeal carcinoma specimens and metastatic lymph nodes from 24 patients were examined for immunohistochemical PCNA expression. The percentages of PCNA positive cells were significantly higher in the primary tumours which developed lymph node metastases than in those without metastases. The fraction of PCNA immunolabelled cells in metastatic lymph nodes increased significantly when compared with the PCNA positive cell score in their corresponding primary tumours obtained from the same patient. There was a significant difference in PCNA index score in primary tumours between the group of patients who survived a 5-year period and those who died within 5 years after treatment. Our data demonstrate that a high proliferation index in primary larynx tumours is retained and increased in corresponding lymph node metastases. Measurement of the fraction of cancer cells stained for PCNA in primary larynx carcinomas can be helpful in selecting tumours with high aggressiveness potential that are more likely to develop neck metastases and thereby in identifying patients who need elective lymph node dissection or additional treatment.


Implementation of Mental Health Centres Pilots in Poland since 2018: A Chance to Move towards Community-Based Mental Health Services.
Provision of mental health care in Poland has long been characterised by an overreliance on psychiatric hospitals and the underdevelopment of community care. The introduction of the first National Mental Health Protection Programme for 2011-2015, with the explicit goal to base provision of mental care on the community mental health centres, failed to achieve any tangible results. The ensuing critique led to the launch of the second National Mental Health Protection Programme for 2017-2022 and the establishment, from mid-2018 onwards, of 41 (33 in operation) mental health centres across Poland. These will be piloted until the end of 2022 but have already shown positive results in terms of access to non-stationary care and a small fall in hospitalisations. They have also performed well during the COVID-19 pandemic, allowing for a quick reorganization of care and continued provision of mental health services. Some of the key innovations of the new model include the introduction of recovery assistants (a new profession) and mental health coordinators (a new role); liaison with social assistance services; and a shift to budget financing. The key obstacles to the national rollout of mental health centres are the low financing of mental health care in Poland, which is among the lowest in Europe, and acute workforce shortages.


Bone GLA protein in predialysis chronic renal failure. Effects of 1,25(OH)2D3 administration in a long-term follow-up.
Serum bone GLA protein (BGP) was measured by radioimmunoassay in 42 patients (age, 47.5 +/- 16.6 years; serum creatinine, 4.32 +/- 1.9 mg/dl) with predialysis chronic renal failure (CRF). Nineteen patients were studied within a short period of time, while 23 were followed with repeated measurements of serum BGP, creatinine, iPTH, and alkaline phosphatase (AP) for a mean period of 17.1 +/- 8.1 months. Eleven of these patients were treated with 1,25(OH)2D3 for a mean of 16.8 +/- 6.4 months. In 23 patients at various stages of CRF, a transiliac bone biopsy was performed for histomorphometric evaluation. In the untreated patients, serum BGP was higher than normal and showed a positive correlation with creatinine levels (P less than 0.001). Serum BGP was also positively correlated with iPTH, AP, serum phosphate, active resorption surface, active osteoblastic surface, osteoid surface, and volume. During treatment with 1,25(OH)2D3, BGP, iPTH, and AP were significantly lower than in the untreated patients. The reduction in iPTH and BGP was proportional, while BGP and AP no longer correlated. Repeated measurements of BGP during the long-term follow-up showed a progressive rise in the untreated patients and a downward course of BGP levels during treatment. In conclusion, serum BGP increases progressively in CRF, rising with advancing renal damage in close correlation with iPTH, AP, and the severity of renal osteodystrophy. Treatment with 1,25(OH)2D3 causes a parallel decline in BGP and iPTH levels and dissociation between BGP and AP can be observed. Compared to AP, BGP seems to be a more reliable index of secondary hyperparathyroidism and potentially more useful in the long-term monitoring of treatment with 1,25(OH)2D3.


[Complications and success rates of subclavian vein catheterization depending on experience].
The infraclavicular puncture of the subclavian vein is a standard procedure for anesthetists. Meanwhile the literature and recommendations are clear and the use of real-time ultrasound guidance is the standard procedure; however, anesthetists will always get into special circumstances were they have to use the landmark technique, so this competence must be preserved. Feared complications of infraclavicular subclavian vein puncture are pneumothorax and arterial puncture. Up to now there is no clear learning curve for the infraclavicular subclavian vein puncture in the landmark technique performed by anesthetists. The aim of this study was to examine the influence of the puncture experience on the success rate and mechanical complications, such as pneumothorax and arterial puncture in patients who received an infraclavicular subclavian vein puncture with the landmark technique. Three levels of experience were defined for comparison: inexperienced 0-20 punctures, moderately experienced 21-50 and experienced over 50 punctures. Post hoc analysis of a previously published noninferiority study to examine the influence of ventilation on the pneumothorax rate in the subclavian vein puncture using the landmark technique. This analysis included 1021 anesthetized patients who were included in the original study between August 2014 and October 2017. Demographic data as well as the number of puncture attempts, puncture success, the overall rate of mechanical complications, pneumothorax rate and arterial puncture rates were calculated. The overall rate of mechanical complications (pneumothorax + arterial puncture) was significantly higher in the inexperienced group (0-21) compared to the experienced group (>50, 15% vs. 8.5%, respectively, p = 0.023). This resulted in an odds ratio of 0.52 (confidence interval, CI: 0.32-0.85, p = 0.027). Likewise, the rate of puncture attempts in the group of inexperienced (0-20) with 1.85 ± 1.12 was significantly higher than in the group of experienced (>50, 1.58 ± 0.99, p = 0.004) and resulted in an odds ratio of 0.59 (CI: 0.31-0.96, p = 0.028). Although the puncture attempts of the moderately experienced (21-50) compared to the inexperienced (0-20) was not significant lower, we found an odds ratio of 0.69 (CI: 0.48-0.99, p = 0.042). The rate of successful puncture was 95.1% in the experienced group versus 89.3% in the inexperienced group (p = 0.001), which resulted in an odds ratio of 2.35 (CI: 1.28-4.31, p = 0.018). When viewed individually, no significant differences were found for pneumothorax and arterial puncture. In this post hoc analysis of the puncture of the subclavian vein using the landmark technique, we found a significant reduction of puncture attempts and overall mechanical complications. At least 50 punctures seem to be necessary to achieve the end of the learning curve; however, the landmark technique should only be used under special circumstances, when real-time ultrasound is not available. Anesthetists who want to complete their repertoire and learn the landmark technique should always perform a static ultrasound examination before starting the puncture in order to reduce complications due to anatomical variations or thrombosis.


Determination of phenols in environmental water samples by two-step liquid-phase microextraction coupled with high performance liquid chromatography.
In this work, a two-step liquid-phase microextraction (LPME) method was presented for the extraction of phenols in environmental water samples. Firstly, the polar phenol in water samples (donor phase) was transferred to 1-octanol (extraction mesophase) by magnetic stirring-assisted LPME. Subsequently, target analytes in the 1-octanol was back extracted into 0.1 mol/L sodium hydroxide solution (acceptor phase) by vortex-assisted LPME. By combination of the two-step LPME, the enrichment factors were multiplied. The main features of this two-step LPME for phenols lie in the following aspects. Firstly, the extraction can be accomplished within relatively short time (ca. 20 min). Secondly, it was compatible with HPLC analysis, avoiding derivatization step that is generally necessary for GC analysis. Thirdly, high enrichment factors (296-954 fold) could be obtained for these analytes. Under the optimized conditions, the linearities were 10-1000, 1-500, 1-500, 5-500 and 1-500 ng/mL for different phenols with all regression coefficients higher than 0.9985. The limits of detection were in the range from 0.3 to 3.0 ng/mL for these analytes. Intra-and inter-day relative standard deviations were below 7.6%, indicating a good precision of the proposed method.


Rheology of sphingans in EPS-surfactant systems.
A model-based rheological characterization of four sphingans in combination with four prominent surfactants of cosmetic formulations of cationic, anionic, zwitterionic and neutral headgroup characteristics was performed. The impact of the surfactants on the rheological properties, based on changes in the mechanical models was evaluated in respect to the closely related structural differences of the polysaccharides, to give an insight on the structure-function relationship of these interactions. The side chains of the sphingans Welan, Diutan and S-88 seem to be involved in the masking of the anionic charge of the polysaccharide backbone, making them highly compatible even with cationic surfactants. The effect of a disaccharide side chain of Diutan also impacts its intermolecular interactions opposed to Welan and S-88, resulting in different surfactant interactions as well as temperature stability. The lack of a side chain in Gellan leads to large incompatibilities with zwitterionic and cationic surfactants due to high polysaccharide-surfactant interactions.


Lipophilic toxicity from the marine dinoflagellate Karenia brevisulcata: use of the brevetoxin neuroblastoma assay to assess toxin presence and concentration.
A method for assessing the presence and concentration of a major toxin produced by Karenia brevisulcata has been developed, based on the neuroblastoma assay for brevetoxins. This cytotoxicity assay, coupled with observations of the dose-response relationship and of changes in cellular morphology during the assay gave a characteristic toxin 'signature'. This signature was consistent whether the toxicity was assessed in extracts of shellfish, seawater samples, uni-algal cultures of K. brevisulcata, or in partially purified toxin samples. Using this method it was possible to confirm the presence of this toxicity during a mixed Karenia bloom, and infer that K. brevisulcata toxin (KBT) was the probable cause of the fish and shellfish mortality observed at that time. The neuroblastoma assay thus provides a solution to the problem of confirming the presence of KBT in suspected K. brevisulcata events, even in the absence of a known toxin structure.


Assisted phytostabilization of soil from a former military area with mineral amendments.
Due to the presence of toxic pollutants, soils in former military areas need remedial actions with environmentally friendly methods. Greenhouse experiments were conducted to investigate the aided phytostabilization of multi-heavy metals (HMs), i.e. Cd, Cr, Cu, Ni, Pb, Zn, in post-military soil by Festuca rubra and three mineral amendments (diatomite, dolomite and halloysite). The amendments were applied at 0 and 3.0% to each pot filled with 5 kg of polluted soil. After seven weeks of the phytostabilization, selected soil properties, biomass yield of F. rubra and immobilization of HMs by their accumulation in plant and redistribution among individual fractions in soil were determined. In addition, ecotoxicology parameters of non-amended and amended soil were established using Phytotoxkit (Sinapsis alba) and Ostracodtoxkit (Heterocypris incongruens) tests. The addition of halloysite significantly increased F. rubra biomass. Diatomite significantly increased both the Cd, Cu, Pb and Cr concentrations in the roots and the pH of the soil. The application of halloysite significantly decreased the Cd and Zn contents of the soil after the completion of the experiment. Dolomite and halloysite were more effective in HM immobilization in soil by decreasing their content in an exchangeable fraction than diatomite. These soil amendments significantly differentiated the length of S. alba roots and had a positive effect on the development of H. incongruens.


Antifreeze glycopeptides of the high-Antarctic silverfish Pleuragramma antarcticum (Notothenioidei).
Antifreeze glycopeptides (AFGP) have been isolated from the fully pelagic high-Antarctic silverfish Pleuragramma antarcticum of the suborder Notothenioidei (Perciformes). The fishes were caught during the PRV Polarstern expedition EPOS III (Jan-Mar, 1989) in the eastern and southeastern Weddell Sea. Glycoconjugate and amino acid analysis of antifreeze glycopeptides (AFGP) indicate that the glycopeptide structure is identical to the polymers of H2N[Ala-Ala(beta-galactosyl(1-->3)-alpha-N- acetylgalactosamine)Thr]nAla-Ala-COOH of previously studied Antarctic notothenioids. The content of AFGPs in P. antarcticum is lower than in other notothenioid fish from the same region. Antifreeze activity shows a maximal hysteresis of 1.19 degrees C at a concentration of 20 mg/ml AFGP. A linear increase in activity of the antifreeze glycopeptides could be demonstrated concomittant with a decreasing ice content. The freezing point of blood serum is -1.9 degrees C.


Comorbid somatic symptoms and functional status in patients with fibromyalgia and chronic fatigue syndrome: sensory amplification as a common mechanism.
Somatic symptoms are common in conditions such as fibromyalgia (FM) and chronic fatigue syndrome (CFS). Authors investigated a potential shared pathologic mechanism: a generalized perceptual abnormality where there is heightened responsiveness to varied sensory stimulation, including pain. A composite measure of sensory sensitivity was created and compared with measures of somatic symptoms, comorbid psychological disturbances, and self-reported physical functioning in 38 patients with FM and/or CFS. Sensory amplification influenced physical functioning indirectly through pain intensity, and physical symptoms and fatigue also independently contributed to physical functioning. Sensory amplification may be an underlying pathophysiologic mechanism in these disorders that is relatively independent of depression and depressive symptoms.


The impact of climate change on Brazil's agriculture.
Brazilian agricultural production provides a significant fraction of the food consumed globally, with the country among the top exporters of soybeans, sugar, and beef. However, current advances in Brazilian agriculture can be directly impacted by climate change and resulting biophysical effects. Here, we quantify these impacts until 2050 using GLOBIOM-Brazil, a global partial equilibrium model of the competition for land use between agriculture, forestry, and bioenergy that includes various refinements reflecting Brazil's specificities. For the first time, projections of future agricultural areas and production are based on future crop yields provided by two Global Gridded Crop Models (EPIC and LPJmL). The climate change forcing is included through changes in climatic variables projected by five Global Climate Models in two emission pathways (RCP2.6 and RCP8.5) participating in the ISIMIP initiative. This ensemble of twenty scenarios permits accessing the robustness of the results. When compared to the baseline scenario, GLOBIOM-Brazil scenarios suggest a decrease in soybeans and corn production, mainly in the Matopiba region in the Northern Cerrado, and southward displacement of agricultural production to near-subtropical and subtropical regions of the Cerrado and the Atlantic Forest biomes.


Shared sorrow, shared costs: cost-effectiveness analysis of the Empowerment group therapy approach to treat affective disorders in refugee populations.
Refugees and asylum seekers (RAS) in Germany need tailored and resource-oriented mental healthcare interventions. To evaluate the cost-effectiveness of group psychotherapy for RAS with moderate depressive symptoms. This is a post hoc cost-effectiveness analysis of Empowerment group psychotherapy that was embedded in a stratified stepped and collaborative care model (SCCM) from the multicentre randomised controlled MEHIRA trial. One hundred and forty-nine participants were randomly assigned to SCCM or treatment as usual (TAU) and underwent Empowerment (i.e. level 3 of the SCCM for adults) or TAU. Effects were measured with the nine-item Patient Health Questionnaire (PHQ-9) and quality adjusted life-years (QALY) post-intervention. Health service and intervention costs were measured. Incremental cost-effectiveness ratios (ICER) were estimated and net monetary benefit (NMB) regressions with 95% confidence intervals were performed. Cost-effectiveness was ascertained for different values of willingness to pay (WTP) using cost-effectiveness acceptability curves for probable scenarios. Trial registration number: NCT03109028 on ClinicalTrials.gov. Health service use costs were significantly lower for Empowerment than TAU after 1 year. Intervention costs were on average €409.6. Empowerment led to a significant change in PHQ-9 scores but not QALY. Bootstrapped mean ICER indicated cost-effectiveness according to PHQ-9 and varied considerably for QALY in the base case. NMB for a unit reduction in PHQ-9 score at WTP of €0 was €354.3 (€978.5 to -€269.9). Results were confirmed for different scenarios and varying WTP thresholds. The Empowerment intervention was cost-effective in refugees with moderate depressive symptoms regarding the clinical outcome and led to a reduction in direct healthcare consumption. Concerning QALYs, there was a lack of confidence that Empowerment differed from TAU.


Preparation and characterization of monoclonal antibodies to enteric adenovirus types 40 and 41.
We have prepared monoclonal antibodies to each of the enteric adenoviruses types 40 and 41. Three different hybridoma cell lines were selected which produced antibody found to react by radioimmunoprecipitation with adenovirus (Ad) hexon antigens. One was specific for Ad 40, another for Ad 41, and a third one reacted with both types. When tested in an enzyme immunoassay against all 41 known human Ad types, the type-specific monoclonal antibody against Ad 40 reacted homotypically, as did the monoclonal antibody against Ad 41. In addition, these monoclonal antibodies neutralized the homologous enteric Ad type. The monoclonal antibody which reacted with both enteric Ad types also showed lower levels of reactivity with the group C adenoviruses types 2, 5, and 6. The monoclonal antibodies produced will provide a definitive means for rapid identification of specific Ad types, and will be useful in defining the relationship of enteric adenoviruses to other types.


Characterization of newfound natural luminescent properties of melamine, and development and validation of a method of high performance liquid chromatography with fluorescence detection for its determination in kitchen plastic ware.
Experimental studies of the natural photoluminescence of melamine in aqueous solutions showed that its fluorescence intensity (at 250/365 nm) was appropriated for analytical purposes. The exploitation of such melamine property provided the basis of development of a new, simple, precise and accurate method based on high performance liquid chromatography with fluorescence detection (HPLC-Fluo) to determine melamine in kitchen plastic ware following aqueous extraction using a microwave oven. Optimization of analytical parameters such as solvent composition, pH and extraction conditions led to limits of detection and quantification of melamine of 0.0081 and 0.027 μg mL(-1), respectively, with a linear range up to 10 μg mL(-1). Sample extracts fortified with melamine at three concentration levels produced an average recovery of 98±6%, which was in agreement with the results achieved with a reference HPLC-UV method. Different samples of kitchen plastic ware analyzed by the developed and optimized method showed melamine concentrations in the aqueous extract up to 17 µg mL(-1), which corresponded to 86.0 mg kg(-1) in these utensils. The results obtained indicate that the use of kitchen plastic ware made of melamine can contaminate food with this compound after heating in a microwave oven.


REM sleep without muscle atonia (stage 1-REM) and its relation to delirious behavior during sleep in patients with degenerative diseases involving the brain stem.
Nocturnal sleep was examined in 12 patients with degenerative diseases involving the brain stem and in 2 patients with late cerebellar cortical atrophy (LCCA). A peculiar sleep state, characterized by the concomitant appearance of a low-voltage mixed frequency EEG, rapid eye movements (REMs) and tonic EMG in mental muscles, repeatedly appeared during nocturnal sleep in all of the 12 patients with degenerative diseases involving the brain stem and it was called stage 1-REM after Tachibana et al. In 8 of the 12 patients, delirious or oneiric behavior appeared during, or soon after, the episodes of stage 1-REM. Inner experiences reported by one of the subjects well corresponded to his behavior during the episode of stage 1-REM. Stage 1-REM was not observed during nocturnal sleep of the patients with LCCA. These results indicate that a degenerative lesion in the brain stem induced stage 1-REM and delirious behavior during nocturnal sleep through abolishing muscle atonia of REM sleep and causing dissociation of the functional components characterizing REM sleep.


Crystal structure of zwitterionic 2-[bis-(2-meth-oxy-phen-yl)phosphanium-yl]-4-methyl-benzene-sulfonate monohydrate di-chloro-methane monosolvate.
In the title compound, C21H21O5PS·H2O·CH2Cl2, the phospho-nium-sulfonate zwitterion has the acidic H atom located on the P atom rather than the sulfonate group. The S-O bond lengths [1.4453 (15)-1.4521 (14) Å] are essentially equal. In the crystal, the water mol-ecules bridge two zwitterions via Owater-H⋯Osulfonate hydrogen bonds into a centrosymmetric dimer. The dimers are further linked by weak CAr-yl-H⋯Osulfonate hydrogen bonds into chains extending along [100]. The PH(+) group is not involved in inter-molecular inter-actions.


Secondary rhinoplasty.
During the past 15 years the guest editor has developed new and better procedures for secondary rhinoplasty. These techniques, including ear cartilage grafts, are discussed in this article.


Covid-19 effects on municipal solid waste management: What can effectively be done in the Brazilian scenario?
The Covid-19 pandemic will leave a lasting impact on nearly every aspect of life in society and has also raised concerns on the contamination risks associated with waste management. This study presents a review on the main recommendations related to the management of municipal solid wastes during the pandemic. The recommendations were classified according to the target audience, and their applicability to the Brazilian reality is discussed. Results show that most analyzed recommendations are related to hygiene routines, use of personal protective equipment, and proper segregation, packing and final destination of potentially contaminated wastes. Brazilian organizations show a special concern about the exposure risks of waste pickers, advising for the temporary suspension of manual waste collection and sorting, hygiene protocols, social distancing and quarantine of recyclable materials. Overall, the recommendations are highly dependent on awareness and engagement of citizens and on planning and support of municipalities, which must invest in information campaigns and provide alternatives for the infectious waste produced in households. Furthermore, this study points out that the recommendations were issued in an emergency scenario, but as the pandemic is expected to last for an extended period of time, they must be revised as local contexts change, seeking to maintain and extend citizens engagement in selective collection and even in actions towards waste reduction.


A Plasmodium falciparum novel gene encoding a coronin-like protein which associates with actin filaments.
Plasmodium falciparum, the major causative agent of human malaria, is an Apicomplexa protozoan parasite which invades in its intermediate host hepatocytes and erythrocytes. The driving force underlying internalization into the host cell is thought to involve both polymerization of parasite actin, as entry is inhibited by the cytochalasins, and an actin motor-associated protein. In the related Apicomplexa parasite, Toxoplasma gondii, the involvement of parasite actin during both processes of motility and host cell entry has been genetically established. In a search for molecules that can regulate actin dynamics within Apicomplexa parasites, we have identified a P. falciparum homologue of the actin associated protein called coronin originally described in the amoeba Dictyostelium discoideum. The single copy gene displays a strong homology with the amoeba sequence and with the bovine and human coronin homologues recently cloned. This homology lies not only within the N-terminus containing the five WD repeats that characterize coronin but also extends in the C-terminal part. Furthermore, using an affinity-purified mouse monoclonal antibody against D. discoideum coronin, we have detected in extracts of P. falciparum young and mature schizonts a 42-kDa polypeptide which binds this antibody and is present in a Triton insoluble fraction that also contains parasite actin filaments. In addition, the recombinant protein encoded by the homologue nucleotidic sequence of P. falciparum coronin is indeed recognized by the antibody against D. discoideum coronin. Finally, the cross-reactive polypeptide displays the ability to cosediment with exogenous F-actin, a property which fits with its involvement in actin dynamics.


The difference-in-difference method: assessing the selection bias in the effects of neighborhood environment on health.
This paper uses the difference-in-difference estimation approach to explore the self-selection bias in estimating the effect of neighborhood economic environment on self-assessed health among older adults. The results indicate that there is evidence of downward bias in the conventional estimates of the effect of neighborhood economic disadvantage on self-reported health, representing a lower bound of the true effect.


Recurrence and complications after sliding inguinal hernia repair.
Sliding hernia is a rare finding and it remains controversial if a laparoscopic or an open (Lichenstein) technique is preferable for repair of sliding hernias. The aim of this study was to investigate the risk of post-operative complications and risk of reoperation due to recurrence in patients with sliding hernia based on surgical technique. The study included male patients receiving hernia repair between 1 January 2010 and 31 December 2017. The data was obtained from the National Danish Hernia Database. A total of 32,396 hernia repairs were included. 13.5% presented with sliding hernia. No difference was found in postoperative complications comparing sliding and non-sliding lateral hernias (5.1% vs 4.2% at 90 days of follow up). Patients treated with a Lichenstein repair had a higher risk of minor complications compared to a laparoscopic repair, however the risk was overall low (1.9% vs 0.8%). Overall 3.1% had surgical repair of recurrence, a higher risk was found among patients with sliding hernia (4.3% vs 2.9%), particularly among those having a Lichenstein repair (OR 2.07, 95% CI 1.11-3.85). A low risk of complications and recurrence after repair of both sliding and non-sliding hernia was found. Among patients with sliding hernia the risk of recurrence was lower in patient having hernia repair using laparoscopic technique although in both groups the risk was low. Sliding hernias can be treated safely using both Lichenstein and laparoscopic techniques.


Bio-inspired polyene cyclization: synthesis of tetracyclic terpenoids promoted by steroidal acetal-SnCl4.
This communication describes a highly efficient intermolecular polyene cyclization method using steroidal acetals as the initiators to synthesize tetracyclic terpenoids; both good yields and good asymmetric induction were obtained.


Endovascular treatment of two pseudoaneurysms originating from the left ventricle.
A 67-year-old woman resented with an acute type A aortic dissection, which was treated surgically with aortic valve replacement as a composite graft with reimplantation of the coronary arteries. At the end of surgery, a left-ventricular venting catheter was placed through the apex and closed with a buffered suture. Consecutive computed tomography (CT) examinations verified a growing apex pseudoaneurysm. Communication between the ventricle and the pseudoaneurysm was successfully closed with an Amplatz septal plug by the transfemoral route. Follow-up CT showed an additional pseudoaneurysm, which also was successfully closed using the same method.


New retinal detachment after pneumatic retinopexy.
Thirteen cases of rhegmatogenous retinal detachment repaired by pneumatic retinopexy were reviewed retrospectively. All patients were followed for a minimum of 6 months after surgery. At the end of follow-up, retinal detachment repair by pneumatic retinopexy succeeded in nine cases (70%) and failed in four (30%). Within 2 days of pneumatic retinopexy, vitreous condensation and traction with new retinal tears and associated detachments in previously uninvolved quadrants developed in two patients. The occurrence of new retinal detachments in the early postoperative period after pneumatic retinopexy has not been previously observed.


Knee strength retention and analgesia with continuous perineural fentanyl infusion after total knee replacement: randomized controlled trial.
Despite providing adequate pain relief, a femoral nerve block can induce postoperative muscle weakness after total knee arthoplasty (TKA). Fentanyl has been shown to have peripheral effects but has not been used as a perineural infusate alone after TKA. Sixty patients scheduled for TKA were randomized to one of three blinded groups: a continuous 24 h infusion of either fentanyl 3 μg/ml, ropivacaine 0.1%, or 0.9% normal saline through a femoral nerve sheath catheter at 10 ml/h. The main outcome was maximum voluntary isometric contraction (MVIC) in the quadriceps femoris (knee extension), measured by a handheld dynamometer (Nm/kg). Other variables assessed were preoperative and postoperative visual analog scale (VAS) scores, hamstrings MVIC (knee flexion), active range of motion of the operative knee, distance ambulated, incidence of knee buckling, supplemental morphine usage, postoperative side effects, and serum fentanyl levels. Quadriceps MVIC values were significantly greater in the fentanyl group compared to the group that received ropivacaine (median values, 0.08 vs. 0.03 Nm/kg; p = 0.028). The incidence of postoperative knee buckling upon ambulation was higher in the ropivacaine group compared to the fentanyl group, although not statistically significant (40% vs. 15 %, respectively; p = 0.077). VAS scores while ambulating were not significantly different between the fentanyl group and the ropivacaine group (p = 0.270). Postoperative morphine consumption, nausea and vomiting, and resting VAS scores were similar among the three groups. A continuous perineural infusion of fentanyl produced greater strength retention than ropivacaine post-TKA.


Emerging role of mesenchymal stromal cells (MSCs)-derived exosome in neurodegeneration-associated conditions: a groundbreaking cell-free approach.
Accumulating proofs signify that pleiotropic effects of mesenchymal stromal cells (MSCs) are not allied to their differentiation competencies but rather are mediated mainly by the releases of soluble paracrine mediators, making them a reasonable therapeutic option to enable damaged tissue repair. Due to their unique immunomodulatory and regenerative attributes, the MSC-derived exosomes hold great potential to treat neurodegeneration-associated neurological diseases. Exosome treatment circumvents drawbacks regarding the direct administration of MSCs, such as tumor formation or reduced infiltration and migration to brain tissue. Noteworthy, MSCs-derived exosomes can cross the blood-brain barrier (BBB) and then efficiently deliver their cargo (e.g., protein, miRNAs, lipid, and mRNA) to damaged brain tissue. These biomolecules influence various biological processes (e.g., survival, proliferation, migration, etc.) in neurons, oligodendrocytes, and astrocytes. Various studies have shown that the systemic or local administration of MSCs-derived exosome could lead to the favored outcome in animals with neurodegeneration-associated disease mainly by supporting BBB integrity, eliciting pro-angiogenic effects, attenuating neuroinflammation, and promoting neurogenesis in vivo. In the present review, we will deliver an overview of the therapeutic benefits of MSCs-derived exosome therapy to ameliorate the pathological symptoms of acute and chronic neurodegenerative disease. Also, the underlying mechanism behind these favored effects has been elucidated.


Neonatal Jaundice: Its Determinants Among Neonates Admitted to Neonatal Intensive Care Units of Tigray Region General Hospitals, Northern Ethiopia.
Background. Despite the significant public health impact of neonatal jaundice on neonatal survival, local epidemiologic data are scarce. Methods. A multi-centered, unmatched case-control study was conducted among 180 consecutively admitted neonates (60 cases and 120 controls). The independent determinants of newborn jaundice were determined using a multivariable binary logistic regression model, and a P-value of <0.05 was used to indicate statistical significance. Results. Maternal medical complications during the index pregnancy (AOR = 2.45; 95% CI 1.01-5.97), rural residence (AOR = 3.1; 95% CI 1.02-9.42), being a low birthweight neonate (AOR = 3.42; 95% CI 1.12-10.41), neonatal B blood group (AOR = 10.19; 95% CI 2.89-35.9), neonatal O blood group (AOR = 2.99; 95% CI 1.04-8.59), and a longer duration of hospital stay (AOR = 9.83; 95% CI 3.11-31.02) were the independent determinants of neonatal jaundice. Conclusions. Early assessment of high-risk neonates might reduce the long-term neurodevelopmental consequences.


Female to male mortality ratios for alcohol-related disorders: possible indicator of susceptibility in different sexes.
We investigated the possibility that organs other than liver in women were more susceptible to alcohol than in men. Female:male cirrhosis mortality ratio in different countries was used as an index of female susceptibility to alcohol. The F:M cirrhosis ratio correlated significantly with F:M ratios for cerebrovascular disease and cancers of the esophagus, liver and lung. This preliminary evidence suggests that other organs and/or disease processes in women may be affected more by alcohol than in men.


Impact of reduced insulin-like growth factor-1/insulin signaling on aging in mammals: novel findings.
Growth hormone deficiency or resistance resulting from spontaneous or experimentally produced mutations in laboratory mice delay aging and increase lifespan. Alterations in insulin-like growth factor-1 (IGF-1) and insulin signaling emerged as likely mechanisms linking growth hormone and aging, and increased longevity was reported in mice with selective deletion of IGF-1 receptor in all tissues or insulin receptor in fat. Recent studies in mice with reduced IGF-1 levels or deletion of pregnancy-associated plasma protein-A, a protease that cleaves one of the IGF-1 binding proteins, strongly support the role of IGF-1 in the control of longevity. Reports of increased lifespan in mice with deletion of insulin receptor substrate (IRS) 1, reduced expression of IRS2, or selective deletion of IRS2 in the brain specifically implicate the IRS-PI3K-Akt-Foxo signaling pathway (which is shared by IGF-1 and insulin) in the control of aging. These important novel findings also strengthen the evidence for evolutionary conservation of mechanisms regulating lifespan in worms, insects and mammals.


Outcomes of bovine versus porcine surgical aortic valve replacement.
There are no guidelines regarding the use of bovine pericardial or porcine valves for aortic valve replacement, and prior studies have yielded conflicting results. The current study sought to compare short- and long-term outcomes in propensity-matched cohorts of patients undergoing isolated aortic valve replacement (AVR) with bovine versus porcine valves. This was a retrospective study utilizing an institutional database of all isolated bioprosthetic surgical aortic valve replacements performed at our center from 2010 to 2020. Patients were stratified according to type of bioprosthetic valve (bovine pericardial or porcine), and 1:1 propensity-score matching was applied. Kaplan-Meier survival estimation and multivariable Cox regression for mortality were performed. Cumulative incidence functions were generated for all-cause readmissions and aortic valve reinterventions. A total of 1502 patients were identified, 1090 (72.6%) of whom received a bovine prosthesis and 412 (27.4%) of whom received a porcine prosthesis. Propensity-score matching resulted in 412 risk-adjusted pairs. There were no significant differences in clinical or echocardiographic postoperative outcomes in the matched cohorts. Kaplan-Meier survival estimates were comparable, and, on multivariable Cox regression, valve type was not significantly associated with long-term mortality (hazard ratio: 1.02, 95% confidence interval: 0.74, 1.40, p = .924). Additionally, there were no significant differences in competing-risk cumulative incidence estimates for all-cause readmissions (p = .68) or aortic valve reinterventions (p = .25) in the matched cohorts. The use of either bovine or porcine bioprosthetic aortic valves yields comparable postoperative outcomes, long-term survival, freedom from reintervention, and freedom from readmission.


Improving the Measurement of Disease Activity for Patients with Rheumatoid Arthritis: Validation of an Electronic Version of the Routine Assessment of Patient Index Data 3.
Introduction. An electronic Routine Assessment of Patient Index Data 3 (RAPID 3) was incorporated into our electronic health records (EHRs) which did not replicate the visual presentation of the paper version. This study validated the electronic RAPID 3 compared to the paper version. Methods. Rheumatoid arthritis (RA) patients (n = 50) completed both the electronic RAPID 3 online in the week prior to and a paper version on the day of their clinic visit. Results. Paired t-test showed no significant difference (p value = 0.46) between versions. Conclusion. The electronic version of RAPID 3 is valid and can be easily integrated in care of RA patients.


Whole-mount immunolocalization to study female meiosis in Arabidopsis.
Here we describe a whole-mount immunolocalization protocol to follow the subcellular localization of proteins during female meiosis in Arabidopsis thaliana, a model species that is used to study sexual reproduction in flowering plants. By using confocal microscopy, the procedure allows one to follow megasporogenesis at all stages before differentiation of the functional megaspore. This in particular includes stages that occur during prophase I, such as the installation of the axial and central elements of the synaptonemal complex along the meiotic chromosomes. In contrast to procedures that require microtome sectioning or enzymatic isolation and smearing to separate female meiocytes from neighboring cells, this 3-day protocol preserves the constitution of the developing primordium and incorporates the architecture of the ovule to provide a temporal and spatial context to meiotic divisions. This opens up the possibility to systematically compare the dynamics of protein localization during female and male meiosis. Steps describe tissue collection and fixation, preparation of slides and polyacrylamide embedding, tissue permeabilization, antibody incubation, propidium iodide staining, and finally image acquisition by confocal microscopy. The procedure adds an essential technique to the toolkit of plant meiotic analysis, and it represents a framework for technical adaptations that could soon allow the analysis of plant reproductive alternatives to sexual reproduction.


Quantitative definition of toxicity: a mathematical description of life and death with dose and time as variables.
This manuscript raises some fundamental issues about the role of time as a variable in toxicology, with implications for all biological sciences and also for disciplines dealing with inanimate systems. The dose-response has taken center stage ever since its formulation by Paracelsus. Time-responses have been considered in the past in various contexts such as time to tumor development or half-life of a compound in an organism. However, there has been, to my knowledge, no successful attempt to tie together dose and time in a generalizable theory. This paper describes toxicity by the minimum number of variables (dose and time) from a macroscopic point of view. Interestingly, these fundamental considerations of the dose- and time-dependence of toxicity led to a simple mathematical formulation, which consists of parts previously recognized as valid under specific conditions of experimentation (Haber's Law of Inhalation Toxicology, Druckrey's Law of Cancer Development).


Structures of (S)-(-)-4-oxo-2-azetidinecarboxylic acid and 3-azetidinecarboxylic acid from powder synchrotron diffraction data.
The crystal structures of the four-membered heterocycles (S)-(-)-4-oxo-2-azetidinecarboxylic acid (I) and 3-azetidinecarboxylic acid (II) were solved by direct methods using powder synchrotron X-ray diffraction data. The asymmetry of the oxoazetidine and azetidine rings is discussed, along with the hydrogen bonding.


Loss of heterozygosity and methylation of p16 in renal cell carcinoma.
To investigate the possible role of genomic aberrations of chromosome 9p21 in the tumorigenesis of human renal cell carcinoma (RCC), 40 sporadic RCCs were studied using PCR analyses. The tumours were predominantly low stage and low grade. Loss of heterozygosity (LOH) was observed in nine of 39 informative cases, but no homozygous deletion was noticed. Hypermethylation of the promoter region of p16 occurred in eight of the 40 RCCs. No correlation was found between hypermethylation of the p16 gene and LOH on 9p21. A similar level of LOH and methylation was observed in the 40 RCCS regardless of histology, grade and stage. These results suggest that inactivation of p16 and the possibility of other unknown tumour suppressor genes located on other chromosomes could be involved in the pathogenesis of RCC.