Left ventricular ischemia in pre-capillary pulmonary hypertension: a cardiovascular magnetic resonance study.
Prognosis in pulmonary arterial hypertension (PAH) is largely dependent on right ventricular (RV) function. However, recent studies have suggested the presence of left ventricular (LV) dysfunction in PAH patients. The potential role of LV ischemia, as a contributor to progressive LV dysfunction, has not been systematically studied in PAH. We aim to assess the presence and extent of LV myocardial ischemia in patients with known PH and without obstructive coronary artery disease (CAD), using oxygen-sensitive (OS) cardiovascular magnetic resonance (CMR) and stress/rest CMR T1 mapping. We prospectively recruited 28 patients with right heart catheter-proven PH and no significant CAD, 8 patients with known CAD and 11 normal age-matched controls (NC). OS-CMR images were acquired using a T2* sequence and T1 maps were acquired using Shortened Modified Look-Locker Inversion recovery (ShMOLLI) at rest and adenosine-induced stress vasodilatation; ΔOS-CMR signal intensity (SI) index (stress/rest SI) and ΔT1 reactivity (stress-rest/rest T1 mapping) were calculated. Global LV ΔOS SI index was significantly lower in PH patients compared with controls (11.1%±6.7% vs. 20.5%±10.5%, P=0.016), as was ΔT1 reactivity (5.2%±4.5% vs. 8.0%±2.9%, P=0.047). The ischemic segments of CAD patients had comparable ΔOS SI (10.3%±6.4% vs. 11.1%±6.7%, P=0.773) to PH patients, but lower ΔT1 reactivity (1.1%±4.2% vs. 5.2%±4.5%, P=0.036). Decreased OS-CMR SI and T1 reactivity signify the presence of impaired myocardial oxygenation and vasodilatory response in PH patients. Given their unobstructed epicardial coronary arteries, this is likely secondary to coronary microvascular dysfunction (CMD).


TSNAdb: A Database for Tumor-specific Neoantigens from Immunogenomics Data Analysis.
Tumor-specific neoantigens have attracted much attention since they can be used as biomarkers to predict therapeutic effects of immune checkpoint blockade therapy and as potential targets for cancer immunotherapy. In this study, we developed a comprehensive tumor-specific neoantigen database (TSNAdb v1.0), based on pan-cancer immunogenomic analyses of somatic mutation data and human leukocyte antigen (HLA) allele information for 16 tumor types with 7748 tumor samples from The Cancer Genome Atlas (TCGA) and The Cancer Immunome Atlas (TCIA). We predicted binding affinities between mutant/wild-type peptides and HLA class I molecules by NetMHCpan v2.8/v4.0, and presented detailed information of 3,707,562/1,146,961 potential neoantigens generated by somatic mutations of all tumor samples. Moreover, we employed recurrent mutations in combination with highly frequent HLA alleles to predict potential shared neoantigens across tumor patients, which would facilitate the discovery of putative targets for neoantigen-based cancer immunotherapy. TSNAdb is freely available at http://biopharm.zju.edu.cn/tsnadb.


Expression of Bcl-2 19-kDa interacting protein 3 predicts prognosis after ampullary carcinoma resection.
An adequate management strategy for ampullary carcinoma (AC), a rare neoplasm, has yet to be determined. The aim of this study was to identify specific molecular markers allowing for the adequate management of AC. The clinicopathological data of 41 patients who underwent curative resection of AC were reviewed retrospectively. The expression of thymidylate synthase (TS) and Bcl-2 19-kDa interacting protein 3 (BNIP3), two sensitive markers for S-1 and gemcitabine, respectively, was evaluated immunohistochemically. The relationship between the expression levels of these markers and the clinicopathological data were then investigated. The 5-year overall survival rate in the study population was 62%. In univariate and multivariate analyses, lymph node metastasis, neural invasion, lymphatic invasion, and the high-level BNIP3 expression were significant predictive factors for a poor postoperative prognosis. Neither TS nor BNIP3 expression were able to predict survival or the disease recurrence rate in patients who received postoperative adjuvant chemotherapy for AC. BNIP3 expression may serve as a prognostic marker for patients with AC, but neither TS nor BNIP3 contributes to the selection criteria for adjuvant chemotherapy for AC, at least with respect to current drug regimens.


Physical habitat in conterminous US streams and rivers, Part 1: Geoclimatic controls and anthropogenic alteration.
Anthropogenic alteration of physical habitat structure in streams and rivers is increasingly recognized as a major cause of impairment worldwide. As part of their assessment of the status and trends in the condition of rivers and streams in the U.S., the U.S. Environmental Protection Agency's (USEPA) National Aquatic Resource Surveys (NARS) quantify and monitor channel size and slope, substrate size and stability, instream habitat complexity and cover, riparian vegetation cover and structure, anthropogenic disturbance activities, and channel-riparian interaction. Like biological assemblages and water chemistry, physical habitat is strongly controlled by natural geoclimatic factors that can obscure or amplify the influence of human activities. We developed a systematic approach to estimate the deviation of observed river and stream physical habitat from that expected in least-disturbed reference conditions. We applied this approach to calculate indices of anthropogenic alteration of three aspects of physical habitat condition in the conterminous U.S. (CONUS): streambed sediment size and stability, riparian vegetation cover, and instream habitat complexity. The precision and responsiveness of these indices led the USEPA to use them to evaluate physical habitat condition in CONUS rivers and streams. The scores of these indices systematically decreased with greater anthropogenic disturbance at river and stream sites in the CONUS and within ecoregions, which we interpret as a response of these physical habitat indices to anthropogenic influences. Although anthropogenic activities negatively influenced all three physical habitat indices in the least-disturbed sites within most ecoregions, natural geoclimatic and geomorphic factors were the dominant influences. For sites over the full range of anthropogenic disturbance, analyses of observed/expected sediment characteristics showed augmented flood flows and basin and riparian agriculture to be the leading predictors of streambed instability and excess fine sediments. Similarly, basin and riparian agriculture and non-agricultural riparian land uses were the leading predictors of reduced riparian vegetation cover complexity in the CONUS and within ecoregions. In turn, these reductions in riparian vegetation cover and complexity, combined with reduced summer low flows, were the leading predictors of instream habitat simplification. We conclude that quantitative measures of physical habitat structure are useful and important indicators of the impacts of human activities on stream and river condition.


Carbon monoxide uptake and excretion: testing assumptions made in deriving the Coburn-Forster-Kane equation.
The Coburn-Forster-Kane equation (CFKE) describes physiological variables that define pulmonary carbon monoxide (CO) uptake and excretion, and carboxyhemoglobin (COHb) levels. This equation is useful in predicting CO uptakes and COHb values in normal humans. However, some assumptions made in its derivation have never been proven and whether or not it accurately describes the physiology of CO excretion is not known. Two assumptions specifically addressed are: that the mean capillary PCO can be computed using the Haldane equation; and that the diffusing capacity relevant to CO uptake is equal to the diffusing capacity relevant to CO excretion. Both assumptions were supported by results obtained in this study. These findings plus results of experiments that compared measured and CFKE-calculated changes in the body CO stores suggest that the CFKE accurately describes the physiology of both pulmonary CO excretion and uptake.


[The evolution of nursing careers, between hope and disillusionment].
The onset of the pandemic has exhausted and disenchanted most hospital professionals. It also seems to have accelerated awareness within the nursing group, particularly among the new "mastered" staff. Working conditions continue to deteriorate and career promises seem to be eroding. Yet in the late 2010s, spokespersons for the nursing occupational group were congratulating themselves on their latest victories. So what happened in such a short time?


Prevalence of undiagnosed asymptomatic bacteriuria and associated risk factors during pregnancy: a cross-sectional study at two tertiary centres in Cairo, Egypt.
The prevalence of asymptomatic bacteriuria (ASB) during pregnancy is poorly understood in Egypt-a country with a high birth rate. To determine the prevalence of ASB among pregnant women booking at El Hussein and Sayed Galal Hospitals in Al-Azhar University in Egypt; and to observe the relationship between ASB prevalence and risk factors such as socioeconomic level and personal hygiene. Obstetrics and gynaecology clinics of 2 university hospitals in the capital of Egypt. Both hospitals are teaching and referral hospitals receiving referrals from across over the country. They operate specialist antenatal clinics 6 days per week. A cross-sectional study combining the use of questionnaires and laboratory analysis was conducted in 171 pregnant women with no signs or symptoms of urinary tract infection (1 case was excluded). Samples of clean catch midstream urine were collected and cultured using quantitative urine culture and antibiotic sensitivity tests were performed. Of 171 pregnant women, 1 case was excluded; 17 cases (10%, 95% CI 5.93% to 15.53%) were positive for ASB. There was a statistically significant relation between the direction of washing genitals and sexual activity per week-and ASB. Escherichia coli was the most commonly isolated bacteria followed by Klebsiella. Nitrofurantoin showed 100% sensitivity, while 88% of the isolates were resistant to cephalexin. The prevalence of ASB seen in pregnant women in 2 tertiary hospitals in Egypt was 10%. E. coli and Klebsiella are the common organisms isolated. The direction of washing genitals and sexual activity significantly influences the risk of ASB. Pregnant women should be screened early for ASB during pregnancy; appropriate treatment should be given for positive cases according to antibiotic sensitivity screening. Cephalexin is likely to be of limited use in this management.


Assessing the risk of viral infection from gases and plumes during intra-abdominal surgery: a systematic scoping review.
The aim of this study was to identify the current evidence regarding the risk of acquiring viral infections from gases or plumes during intra-abdominal surgery. Peritoneal fluids may contain cellular material and virus particles. Electrocautery smoke and plumes from energy devices may aerosolize harmful substances and viral particles. Insufflation and desufflation during laparoscopic surgery may also aerosolize and distribute biological material. A systematic scoping review was performed to assess the evidence and inform safe surgical practice. A systematic search of the PubMed and Medline databases was undertaken until June 2020, observing Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology, to identify articles associating viral infection of operating room staff from surgical gases and plumes. All evidence levels were included. The search strategy utilized the search terms 'surgery', 'laparoscopy', 'laparoscopic' 'virus', 'smoke', 'risk', 'infection'. The literature search identified 74 articles. Eight articles relevant to the subject of this review were included in the analysis, two of which specifically related to intra-abdominal surgery. Of the remaining six, four involved gynaecological surgery and two were in-vitro studies. No evidence that intra-abdominal surgery was associated with an increased risk of acquiring viral infections from exsufflated gas or smoke plumes was identified. There is currently no evidence that respiratory viruses can be found in the peritoneal fluid. Whilst there is currently no evidence that desufflated carbon dioxide or surgical smoke plumes present a significant infectious risk, there is not a wealth of literature to inform current practice. Further clinical research in this area is required.


Announcing the diagnosis: counselling the parents.
Diagnosis appears as a triumph, crucial for further therapeutic endeavors. Yet, what is said may be misunderstood. New, even helpful, diagnosis may be disturbing. All we have is information. It is necessary to know the person and to understand the context in which diagnosis is given, by a senior, in privacy. What may seem "good news" to the neurologist may be tempered by the scale of the ordeal that has to be faced by the child and family. To understand the frustration of the parents obliges us to look at some of the motives for having children. The stages of grief are shock, denial, depression, guilt, and coming to terms. "Psychological defences" consists of repression, denial, projection, displacement, rationalization, and sublimation. Diagnosis represents a potential major and irreversible life change. As for any other medical act, announcing to parents that their child has severe neurological sequelae consists of an irreversible decision in which the physician is often faced with situations for which written regulations are clearly insufficient. Indeed, moral duty dictates injunctions that pull the decision in opposite directions: loyalty in announcing a terrible truth but protection from dreadful moral sufferance.


A systematic approach for developing mechanistic models for realistic simulation of cancer cell motion and deformation.
Understanding and predicting metastatic progression and developing novel diagnostic methods can highly benefit from accurate models of the deformability of cancer cells. Spring-based network models of cells can provide a versatile way of integrating deforming cancer cells with other physical and biochemical phenomena, but these models have parameters that need to be accurately identified. In this study we established a systematic method for identifying parameters of spring-network models of cancer cells. We developed a genetic algorithm and coupled it to the fluid-solid interaction model of the cell, immersed in blood plasma or other fluids, to minimize the difference between numerical and experimental data of cell motion and deformation. We used the method to create a validated model for the human lung cancer cell line (H1975), employing existing experimental data of its deformation in a narrow microchannel constriction considering cell-wall friction. Furthermore, using this validated model with accurately identified parameters, we studied the details of motion and deformation of the cancer cell in the microchannel constriction and the effects of flow rates on them. We found that ignoring the viscosity of the cell membrane and the friction between the cell and wall can introduce remarkable errors.


The incidence and use of Oryctes virus for control of rhinoceros beetle in oil palm plantations in Malaysia.
The rhinoceros beetle, Oryctes rhinoceros, has emerged as a serious pest of oil palm since the prohibition of burning as a method for maintaining estate hygiene in the 1990s. The abundance of beetles is surprising given that the Malay peninsula was the site of first discovery of the Oryctes virus, which has been used to effect good as a biological control agent in other regions. A survey of adult beetles was carried out throughout Malaysia using pheromone traps. Captured beetles were examined for presence of virus using both visual/microscopic examination and PCR detection methods. The survey indicated that Oryctes virus was common in Malaysia among the adult beetles. Viral DNA analysis was carried out after restriction with HindIII enzyme and indicated at least three distinct viral genotypes. Bioassays were used to compare the viral strains and demonstrate that one strain (type B) is the most virulent against both larvae and adults of the beetle. Virus type B has been cultured and released into healthy populations where another strain (type A) forms the natural background. Capture and examination of beetles from the release site and surrounding area has shown that the spread and persistence of the applied virus strain is accompanied by a reduction in palm frond damage.


Etiology and consequences of respiratory failure in thermally injured patients.
Inhalation injury predisposes burn patients to pneumonia, respiratory failure, and death, but the incidence and consequences of respiratory failure in the absence of inhalation injury are not well known. In a review of 529 burn patients admitted over a 4-year period, patients with inhalation injury had a 73% incidence of respiratory failure (hypoxemia, multiple pulmonary infections, or prolonged ventilator support) and a 20% incidence of adult respiratory distress syndrome (ARDS). In patients without inhalation injury, respiratory failure developed in 5% of patients and ARDS in 2% (both p < 0.001). Patients with respiratory failure display a high incidence of multiple organ failure and mortality (27% to 50%), regardless of the presence of inhalation injury. All patients who died had multiple organ failure. This review demonstrates that respiratory failure, regardless of its cause, frequently leads to multiple organ failure and death. Inhalation injury, in the absence of respiratory failure, does not appear to contribute to mortality.


Vanadate ions: central nervous system action on glucoregulation.
Vanadate (VO-3), an essential trace element with insulin-mimetic actions, produces systemic hyperglycemia following central administration in mice. The hyperglycemic effect is due to specific action of vanadate or its reduced form, vanadyl (VO2+); other ions of similar atomic weight (Cr, Mn) or structure (phosphate) have no effect. The effect of central vanadate to raise circulating glucose is blocked by coadministration of 3-O-methylglucose or polymyxin B, which prevent insulin- and vanadate-stimulated glucose transport. Finally, the central hyperglycemic effect is prevented by treatments which block sympathetic outflow from the CNS or diminish the levels of circulating epinephrine. These results show that vanadate is able to influence peripheral glucoregulation by increasing sympathetic outflow from the CNS. Moreover, they suggest that this effect is linked to action of VO-3 or its reduced form, VO2+, to stimulate glucose transport into neuronal cells.


Spectrum of genomic alterations in FGFR3: current appraisal of the potential role of FGFR3 in advanced urothelial carcinoma.
Molecular analysis has identified subsets of urothelial carcinoma (UC) expressing distinct genetic signatures. Genomic alterations in the oncogenic fibroblast growth factor receptor 3 (FGFR3) pathway are among the most well described in UC and have led to extensive and ongoing investigation of FGFR3-targeted therapies in this disease, although no new drugs have yet been approved. Given the unmet need for effective treatments in advanced and metastatic UC, a better understanding of the known molecular alterations of FGFR3 and of the previous and ongoing clinical investigations of this promising target in UC deserves attention. The objective of the present review is to describe the landscape of alterations and biology of FGFR3 in UC, comprehensively summarize the current state of UC clinical trials of FGFR3 inhibitors, and discuss future therapeutic applications. Using the Pubmed and Clinicaltrials.gov databases, articles describing the spectrum and biological activity of FGFR3 genomic alterations and trials of FGFR3 inhibitors in UC were identified. Search terms included 'FGFR3 genomic alterations' and 'urothelial cancer' or 'bladder cancer'. Genomic alterations, including translocations and activating mutations, are increasingly described in advanced and metastatic UC. The majority of clinical trials have been performed in unselected populations; however, recent studies have reported encouraging preliminary data. We argue that routine use of molecular genomic tumour analysis in UC may inform selection of patients for appropriate trials and we further investigate the potential of FGFR3 as a meaningful clinical target for this difficult disease.


Assessment of quality of life in the supportive care setting of the big lung trial in non-small-cell lung cancer.
The Big Lung Trial (BLT) was a large, pragmatic trial to evaluate the addition of chemotherapy to primary treatment (ie, surgery, radical radiotherapy, or supportive care) in non-small-cell lung cancer (NSCLC). In the supportive care group, there was a small but significant survival benefit in patients treated with chemotherapy compared with supportive care alone (no chemotherapy). A substudy was undertaken to evaluate the quality of life (QoL) implications of the treatment options. QoL was assessed using European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaires C30 (QLQ-C30) and LC17, and daily diary cards. EORTC QLQ-C30 and LC17 were collected at 0, 6 to 8, 12, 18, and 24 weeks. Diary cards were completed during the first 12 weeks of the study. The primary end point was global QoL at 12 weeks. A total of 273 patients were randomly assigned: 138 to no chemotherapy and 135 to chemotherapy. There was no evidence of a large detrimental effect on QoL of chemotherapy. No statistically significant differences in global QoL or physical/emotional functioning, fatigue and dyspnea, and pain were detected at 12 weeks. Higher rates of palliative radiotherapy in the no chemotherapy arm may have lessened differences in QoL. Global QoL, role functioning, fatigue, appetite loss, and constipation were prognostic indicators of survival at 12 weeks. There were no important adverse effects of chemotherapy on QoL.


Fas ligand is present in tumors of the Ewing's sarcoma family and is cleaved into a soluble form by a metalloproteinase.
Fas ligand (FasL) exists in transmembrane and soluble forms and induces apoptosis on cross-linking with the Fas receptor. We evaluated the biological significance of FasL and Fas in 61 tumor tissues and 9 cell lines of the Ewing's sarcoma family of tumors (ESFT). FasL was present in 62.5% and Fas in 79.4% of primary ESFT. Metastatic tumors had higher expression of FasL (95%), suggesting association with a metastatic phenotype. FasL was detected in the cytoplasm and membrane of ESFT cells by immunofluorescence. Western blotting revealed transmembrane and soluble FasL in cytosolic extracts and soluble FasL in conditioned media. Both transmembrane and soluble FasL induced apoptosis of Fas-sensitive Jurkat cells in co-culture experiments with ESFT cells or their media. Treatment with phenanthroline and the synthetic metalloproteinase inhibitor BB-3103 reduced the levels of soluble FasL in the media, suggesting that in ESFT, FasL is processed by a metalloproteinase and released in the extracellular milieu. The released soluble FasL may serve to attack cells of the immune system and/or interfere with the binding of transmembrane FasL with Fas, and results in down-regulation of transmembrane FasL. Synthetic metalloproteinase inhibitors may modify the ratio of transmembrane to soluble FasL.


Restless Legs Syndrome, and symptoms of Restless Syndrome in patients with Graves' disease: a cross-sectional survey.
Restless legs syndrome (RLS) is a frequent comorbid condition associated with distinct unrelated diseases. While the incidence of RLS has not been definitively confirmed, RLS-like symptoms have been reported in a section of Asian population who also had hyperthyroidism. The prevalence of RLS is generally low in Asian populations. Under these circumstances, we hypothesized that in a population where RLS is common, such as in Brazil, RLS could manifest as a comorbid ailment alongside Graves' disease, a common hyperthyroid condition. In a cross-sectional survey, 108 patients who presented with Graves' disease were analyzed for restless legs or associated symptoms. Twelve patients (11.1%) displayed symptoms of RLS prior to the incidence of Graves' disease. These patients experienced worsening of the symptoms during their hyperthyroid state. Six patients (5.6%) developed RLS, consequent upon the incidence of Graves' disease as per the consensus of the panel of the experts. Fifteen patients (13.9%) also presented with RLS-like symptoms without any discernible circadian feature of the syndrome. Our findings confirm that Graves' disease might trigger restless legs-like symptoms, while the condition of hyperthyroidism could also be complicated by definite RLS.


Adenomas of the gallbladder. Morphologic features, expression of gastric and intestinal mucins, and incidence of high-grade dysplasia/carcinoma in situ and invasive carcinoma.
We report 201 gallbladder adenomas from 91 patients most of whom were adult females. Fifty-three (58%) patients had gallstones. In 83 (91%) patients the adenomas were single. One gallbladder had 102 adenomas. Histologically, 165 (82%) of 201 adenomas were classified as pyloric, 28 (14%) as intestinal, 5 (2.4%) as foveolar, and 3 (1.4%) as biliary. Two patients had intestinal-type adenomas coexisting with biliary papillomatosis. Twenty-eight percent of pyloric gland adenomas contained squamoid morules. Two pyloric gland adenomas were composed predominantly of columnar oxyphil cells. High-grade dysplasia/carcinoma in situ was identified in 44 (27%) of 165 pyloric gland adenomas and low-grade dysplasia in 25 (15%) of 165. However, only 2 (1%) invasive adenocarcinomas, both of intestinal type, arose in pyloric gland adenomas. Both patients survived more than 5 years. Intestinal-type adenomas were classified as tubular, papillary, and tubulopapillary. High-grade dysplasia/carcinoma in situ was recognized in 13 (46%) of 28 intestinal adenomas. However, only 1 (3.5%) invasive adenocarcinoma with biliary phenotype arose in an intestinal-type adenoma. Foveolar adenomas showed low-grade dysplasia, and biliary adenomas were composed of columnar cells similar to the normal biliary cells of the gallbladder. None of these tumors progressed to adenocarcinoma. MUC5AC and MUC6 labeled 44 (95%) of 46 pyloric gland adenomas, whereas CDX2 was positive in 14 (78%) of 18 intestinal adenomas and MUC2 in 6 (33%) of 18. MUC5AC and MUC6 labeled 2 foveolar adenomas, and 2 biliary adenomas expressed only CK7. The immunophenotype of gallbladder adenomas justifies their classification into pyloric, intestinal, foveolar, and biliary. Our results indicate that adenomas of the gallbladder play a minor role in the pathway of gallbladder carcinogenesis.


Analyzing free-text survey responses: An accessible strategy for developing patient-centered programs and program evaluation.
Despite widespread availability of yoga in the Veterans Health Administration (VA), it remains unclear how to best evaluate yoga programs. This is particularly problematic for programs aimed at veterans with mental health concerns, as evaluation typically focuses narrowly upon mental health symptom severity, even though program participants may have other health-related priorities. We analyzed responses to free-text questions on 237 surveys completed by veterans with mental health concerns enrolled in a yoga program at six VA clinics in Louisiana to characterize veteran participants' experiences with yoga. Qualitative analysis resulted in 15 domains reflecting veterans' individual health-related values and priorities. We use results to illustrate the potential for analysis of free-text responses to reveal valuable insights into patient experiences, demonstrating how these data can inform patient-centered program evaluation. The approach we present is more accessible to those responsible for decision-making about local programs than conventional methods of analyzing qualitive evaluation data.


Mechanisms of metal sorption by biochars: Biochar characteristics and modifications.
Biochar produced by thermal decomposition of biomass under oxygen-limited conditions has received increasing attention as a cost-effective sorbent to treat metal-contaminated waters. However, there is a lack of information on the roles of different sorption mechanisms for different metals and recent development of biochar modification to enhance metal sorption capacity, which is critical for biochar field application. This review summarizes the characteristics of biochar (e.g., surface area, porosity, pH, surface charge, functional groups, and mineral components) and main mechanisms governing sorption of As, Cr, Cd, Pb, and Hg by biochar. Biochar properties vary considerably with feedstock material and pyrolysis temperature, with high temperature producing biochars with higher surface area, porosity, pH, and mineral contents, but less functional groups. Different mechanisms dominate sorption of As (complexation and electrostatic interactions), Cr (electrostatic interactions, reduction, and complexation), Cd and Pb (complexation, cation exchange, and precipitation), and Hg (complexation and reduction). Besides sorption mechanisms, recent advance in modifying biochar by loading with minerals, reductants, organic functional groups, and nanoparticles, and activation with alkali solution to enhance metal sorption capacity is discussed. Future research needs for field application of biochar include competitive sorption mechanisms of co-existing metals, biochar reuse, and cost reduction of biochar production.


Prevalence of Painful Diabetic Neuropathy Using the Self-Completed Leeds Assessment of Neuropathic Symptoms and Signs Questionnaire in a Population with Diabetes.
This study assessed the feasibility of diagnosing painful diabetic neuropathy (PDN) using a postal self-completed Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS) questionnaire, and it compared the prevalence of PDN in patients with diabetes attending primary and secondary care. This was an observational study in northwest England, United Kingdom (n=204). S-LANSS were used by post to diagnose PDN. Consent for participation and access of blood results were obtained from the subjects with diabetes. Ethical approval was granted to do the work. In this study the prevalence of PDN was 30.3%, comprising 33.1% of patients with type 2 diabetes compared to 14.1% patients with type 1 diabetes. The overall prevalence of PDN was 33% (n=43) in the secondary care group and 25.6% (n=19) in the primary care group; the rates were not statistically significant. There were no gender differences between the primary and secondary care populations. There was a significant association of obesity, smoking and height in males with PDN compared to the non-PDN group (p<0.05). There was a significant trend toward increasing prevalence of PDN with duration of diabetes, increasing glycated hemoglobin and increasing body mass index (p<0.05). The overall prevalence of PDN in this study was 30.3%. The results demonstrated the use of self-administered S-LANSS was easy and can be used for epidemiologic surveys of PDN. The results are comparable to and similar to other published series, in both primary and secondary care settings.


Muscle derived stem cell therapy for stress urinary incontinence.
The aim of this article is to discuss the potential of muscle-derived stem cells (MDSCs) for rhabdosphincter regeneration and to review the early clinical experiences with its application in patients with stress urinary incontinence. In anatomical and functional studies of the human and animal urethra, the middle urethral contained rhabdosphincter is critical for maintaining continence. Transplanted stem cells have the ability to undergo self-renewal and multipotent differentiation, leading to sphincter regeneration. In addition, such cells may release, or be engineered to release, neurotrophins with subsequent paracrine recruitment of endogenous host cells to concomitantly promote a regenerative response of nerve-integrated muscle. Cell-based therapies are most often associated with the use of autologous multipotent stem cells, such as bone marrow stromal cells. However, harvesting bone marrow stromal stem cells requires a general anesthetic, can be painful, and has variable yield of stem cells upon processing. In contrast, with appropriate experience, alternative autologous adult stem cells such as muscle-derived stem cells and adipose-derived stem cells can be obtained in large quantities and with minimal discomfort.


Bioinformatic screening and experimental analysis identify SFRP1 as a prognostic biomarker for tongue squamous cell carcinomas.
To provide a prognostic biomarker and a potential therapeutic target for tongue squamous cell carcinoma (TSCC). Screening the prognostic genes of TSCC by bioinformatics, and verifying the correlation between the above genes and the prognosis of TSCC by experiments. Twenty-four common differentially expressed genes (DEGs) between TSCC and the corresponding normal tissues were screened from four sets of TSCC functional gene expression series in Gene Expression Omnibus (GEO) datasets. Further bioinformatics research based on the data from The Cancer Genome Atlas (TCGA), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) indicate that the low expression of SFRP1 might be correlated with poor prognosis of TSCC patients. By colony formation assay, reverse transcription polymerase chain reaction (RT-PCR), western blotting, immunohistochemical staining, flowcytometry, lentivirus transfection and animal experiments, it was confirmed that the low level of SFRP1 expression correlated with poor prognosis of TSCC patients. This study identified SFRP1 as a novel prognostic biomarker and a potential therapeutic target for TSCC.


Socio-economic deprivation and excess winter mortality and emergency hospital admissions in the South Yorkshire Coalfields Health Action Zone, UK.
The aims of this study were to describe the pattern of excess winter mortality and emergency hospital admissions in the South Yorkshire Coalfields Health Action Zone, and to examine the relationship between excess winter mortality and emergency hospital admissions and socio-economic deprivation at the enumeration district level. We analysed monthly deaths from 1981 to 1999 and monthly emergency hospital admissions from 1990 to 1999 for cardiovascular disease, respiratory disease and all other causes of death for people aged 45 years and above. We used the enumeration district level Townsend socio-economic deprivation score to categorize enumeration districts by quintile. Excess winter mortality ratios (observed/expected) for females and males, respectively, were 1.70 and 1.58 for respiratory disease, 1.25 and 1.20 for cardiovascular disease, and 1.09 and 1.07 for all other causes of death. The excess winter hospital admission ratio for respiratory disease was 1.80 for females and 1.58 for males. No excess was evident for the other two groups of conditions. We found no significant increase in excess winter mortality ratios with increasing socio-economic deprivation. There was also no significant increase in the excess winter respiratory admission ratio with increasing deprivation. With regard to age, we found P<0.0001 and for all other diseases P>0.001 and also in the excess winter hospital admission ratio for respiratory disease P<0.0001 With regard to sex, the excess ratios were lower in men than in women for both respiratory mortality P<0.05 and respiratory hospital admissions P<0.0001 We also observed that excess winter mortality ratios decreased significantly over the 18-year period for cardiovascular disease P<0.05 and for all other diseases P<0.05. Our results suggest that measures to reduce excess winter mortality should be implemented on a population-wide basis and not limited to socio-economically deprived areas. There may also be a case for tailoring interventions to specifically meet the needs of older people.


Tremor frequency characteristics in Parkinson's disease under resting-state and stress-state conditions.
Tremor characteristics-amplitude and frequency components-are primary quantitative clinical factors for diagnosis and monitoring of tremors. Few studies have investigated how different patient's conditions affect tremor frequency characteristics in Parkinson's disease (PD). Here, we analyzed tremor characteristics under resting-state and stress-state conditions. Tremor was recorded using an accelerometer on the finger, under resting-state and stress-state (calculation task) conditions, during rest tremor and postural tremor. The changes of peak power, peak frequency, mean frequency, and distribution of power spectral density (PSD) of tremor were evaluated across conditions. Patients whose tremors were considered more than "mild" were selected, for both rest (n=67) and postural (n=25) tremor. Stress resulted in both greater peak powers and higher peak frequencies for rest tremor (p<0.001), but not for postural tremor. Notably, peak frequencies were concentrated around 5 Hz under stress-state condition. The distributions of PSD of tremor were symmetrical, regardless of conditions. Tremor is more evident and typical tremor characteristics, namely a lower frequency as amplitude increases, are different in stressful condition. Patient's conditions directly affect neural oscillations related to tremor frequencies. Therefore, tremor characteristics in PD should be systematically standardized across patient's conditions such as attention and stress levels.


Effects of the novel HPPD-inhibitor herbicide QYM201 on enzyme activity and microorganisms, and its degradation in soil.
QYM201 is a 4-hydroxyphenylpyruvate dioxygenase (HPPD) inhibiting herbicide recently registered in China for controlling grass and broadleaf weeds in wheat. It is a novel herbicide, and its potential harm to soil ecosystems has not yet been reported. This study investigates the influence of QYM201 on soil enzyme activity and microorganism quantities in two different soils at concentrations of 0.1, 1, and 5 mg kg-1 soil. Results indicate that QYM201 initially inhibited soil protease, urease, and sucrase activity and this effect increased with concentration. During the later stages of incubation, inhibitory effects gradually weakened and by the end of the experiment (45 days), enzyme activity was restored to control levels. Catalase activity was stimulated by QYM201, with significant differences observed between the QYM201-treated groups and the control at the onset of exposure. This stimulation effect decreased during the later stages of the experiment. However, catalase activity was still significantly higher at the end of the experiment compared to the control. The effects of QYM201 on soil microorganisms differed. Initially, bacteria and actinomycetes quantities were decreased by QYM201 (10 days). As the incubation progressed, microorganism quantities in the lower concentration groups (0.1 and 1 mg kg-1 soil) were restored to control levels, while those of the high concentration group (5 mg kg-1 soil) did not fully recover. QYM201 did not significantly impact the quantity of fungi. The half-life and degradation rate constant (k) of QYM201 for the two studied soil types were 23.1 days and 16.1 days, and 0.030 and 0.043 day-1, respectively.


Visualizable intracardiac flow pattern in fetuses with congenital heart defect: pilot study of blood speckle-tracking echocardiography.
Blood-flow pattern is an essential factor in cardiovascular development. Recently, blood speckle-tracking echocardiography (BST) based on high-frame-rate ultrasound has emerged as a promising technique for the assessment of blood-flow patterns and properties. The objectives of this study were to determine the feasibility of BST in the fetus and to assess intracardiac blood-flow patterns of fetuses with a congenital heart defect (CHD) using this technique. This was a prospective study consisting of 35 normal fetuses, 35 fetuses with left-sided obstructive lesion (LSOL) and 35 fetuses with right-sided obstructive lesion (RSOL). BST images of fetal intracardiac regions of interest (ROIs), including the left ventricle (LV), right ventricle (RV), ascending aorta (AAo), aortic arch (AA), descending aorta (DAo) and pulmonary artery (PA), were obtained and analyzed. The feasibility of BST was assessed, and blood-flow pattern and number of vortices in the ROIs were recorded. The median gestational age of the fetuses was 24.7 weeks (range, 19.6-34.3 weeks). BST was feasible in 81.6% of cases, and the cut-off value of depth for an adequate BST image was ≤ 7.9 cm. There were no differences in the presence of vortex/turbulent blood flow in the LV or RV among the three groups. Vortex/turbulent blood flow in the AAo was detected in 0% (0/35), 14.3% (5/35) and 57.1% (20/35) of cases in the control, LSOL and RSOL groups, respectively. The respective values were 5.7% (2/35), 14.3% (5/35) and 51.4% (18/35) for the AA; 0% (0/35), 48.6% (17/35) and 0% (0/35) for the DAo; and 0% (0/35), 40.0% (14/35) and 51.4% (18/35) for the PA. With the exception of the DAo in the RSOL group, vortex/turbulent flow in the great artery ROIs was significantly more common in the LSOL and RSOL groups than in controls (P < 0.01). In the LSOL group, the number of vortices in the AAo, AA, DAo and PA was significantly greater compared with that in controls (P < 0.01). In the RSOL group, the number of vortices in the LV, AAo, AA and PA was significantly greater compared with that in controls (P < 0.01). Fetuses with CHD were more likely to exhibit vortex/turbulent blood flow and increased number of vortices in the great arteries compared with healthy controls. Further research is needed to determine the biomechanical effect of blood-flow patterns, especially vortex flow, on fetal cardiovascular structure and function. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.


Ornithine decarboxylation in rat liver nuclei.
1. Decarboxylation of ornithine in rat liver cytosol produces putrescine; on the contrary, no putrescine is formed in nuclei. 2. In nuclei, decarboxylation is not inhibited by alpha-difluoromethylornithine and depends on NADH reoxidation. This shows that decarboxylation occurs after transamination of ornithine. 3. The increase of ornithine transaminase activity may be partially responsible for the enhanced decarboxylation after 1-methyl-3-isobutylxanthine administration. Data obtained in the presence of Ca2+ suggest that modification of nuclear Ca2+ concentration may also be responsible.


Academy of Nutrition and Dietetics: 2020 Cystic Fibrosis Evidence Analysis Center Evidence-Based Nutrition Practice Guideline.
The Academy of Nutrition and Dietetics Evidence Analysis Center conducted a systematic review of the literature to develop an evidence-based practice guideline for primary nutrition issues in cystic fibrosis (CF). This guideline is designed to complement and build upon existing evidence-based CF nutrition guidelines. The objective of this guideline was to provide recommendations for registered dietitian nutritionists in the United States delivering medical nutrition therapy to individuals with CF and their families that fill gaps in current evidence-based guidelines on topics that are crucial in order to improve health and prevent disease progression. This guideline provides 28 nutrition recommendations to guide medical nutrition therapy, including nutrition screening, nutrition assessment, and dietary intake. For topics outside the scope of this guideline, practitioners are referred to external, evidence-based recommendations. The CF landscape is evolving rapidly with breakthroughs in cystic fibrosis transmembrane regulator modulators changing CF at a cellular level. Medical nutrition therapy for individuals with CF from infancy through advanced age requires novel and individualized approaches. The Academy Evidence Analysis Library CF guidelines provide a framework for expanding upon current knowledge to determine effective nutrition strategies for individuals with CF through long and healthy futures.


Balloon angioplasty versus stent placement for the treatment of portal vein stenosis in children: a single center experience.
To evaluate the safety and efficacy of percutaneous interventional treatment of portal vein stenosis in children. A retrospective analysis of all interventional treatments for portal vein stenosis in pediatric patients at a single institution from 2010 to 2021 was conducted. Platelet count, spleen size and portal vein flow velocity were assessed during the follow-up period. Primary and primary assisted patency time were determined. A total of ten children (median age 28.5 months, interquartile range (IQR): 2.75-52.5 months) with portal vein stenosis after Mesorex-Shunt (n = 4), liver transplantation (n = 3) and other etiologies (n = 3) underwent 15 interventional procedures. There were five reinterventions and one discontinued intervention. The technical success rate was 93.3% (14/15) and clinical success of treated patients was 100% (14/14). Median follow-up was 18 months (IQR: 13.5-81 months). The median primary patency time for stent placement was 70 months (IQR: 13.5-127.25 months). For balloon angioplasty, the median primary patency time was 9 months (IQR 7.25-11.5 months), while the median assisted primary patency time was 14 months (IQR: 12 to 15 months). Platelet count, spleen size and portal vein flow velocity reliably corresponded to recurrence of portal vein stenosis in asymptomatic patients during follow-up. Interventional treatment is a safe and efficient method to treat portal vein stenosis with long patency times, regardless of etiology. Primary stent placement shows a higher primary patency time than balloon angioplasty. Implementation of stent placement as the primary interventional method may improve patency times and reduce the need for repeat reinterventions in pediatric patients.


Working with oocyte nuclei: cytological preparations of active chromatin and nuclear bodies from amphibian germinal vesicles.
The giant nucleus or germinal vesicle (GV) of amphibian oocytes presents a remarkable opportunity to examine nuclear structures in unprecedented levels of detail. By making use of spread preparations of GVs, it is possible to investigate the structure and function of transcription units in active chromatin and a variety of nuclear bodies, all within the limits of resolution of the light microscope. The basic method for producing GV spreads that is described here is based on simple manual dissection and, therefore, it permits the preparation of nuclear components that have suffered a minimum of experimental manipulation. The particular method described is based on the use of oocytes from a salamander, the axolotl, although the approach is robust and applicable with minor modification to two other model amphibian species, Xenopus laevis and X. tropicalis. One common approach to investigating the molecular organisation of oocyte nuclear structures by immunofluorescent staining of endogenous or exogenous polypeptides is also described.


[Method establishment for the determination of 6 organophosphorus pesticides metabolites in human urine using LC-MS/MS].
To establish a method to determine the presence and concentration of DEP, DMDTP, DEDTP, PNP, CMHC and TCPY organophosphorus pesticides metabolites in human urine by LC-MS/MS. 2.0 ml of urine was enzymatically hydrolyzed in water bath 37 degrees C for 4 hours, then the urine samples were solid-phase extracted by Oasis HLB and eluted with methanol, after centrifugation and concentration the urine samples were separated on waters symmetry C18 5 microm (2.1 mm x 150 mm) column with ammonium acetate buffer solution acetonitrile-water as mobile phase to constant gradient elution. Electrospray ionization source (ESI) was applied and operated in positive ion mode, and multiple reaction monitoring (MRM) mode was adopted. Within concentration ranging from 0 - 1000 ng/ml the correlation coefficient for 5 compounds of 6 were greater than 0.990, recoveries were between 79% - 130%, RSD < 8.2%. The RSD of intra-day and inter-day were less than 15% (n = 6). The procedure of samples collection is simple. This is a accurate and specific method for testing organophosphorus pesticides metabolites in human urine.


Endoscopic submucosal dissection for large colorectal tumors using a cross-counter technique and a novel large-diameter balloon overtube.
Endoscopic submucosal dissection (ESD) in early gastric cancer (EGC), which provides a higher complete resection rate than conventional endoscopic mucosal resection (EMR), has rapidly come into widespread use. However, colorectal ESD is not widely used because of its technical difficulty and complications such as perforation, and the procedure time is longer than that of conventional EMR. Development of safer and more reliable devices as well as technique modifications are therefore required. The aim of our study is to compare safety and efficacy of a new traction method, the cross-counter technique, for large colorectal tumors combined with a balloon overtube. A total of 30 patients with large colorectal tumors were analyzed retrospectively; 15 patients for the cross-counter technique group (CC group) and 15 patients for the no-traction group (NT group). Procedure time, complete resection rate, perforation rate and bleeding rate were assessed. The procedure time was 126 ± 42.2 min and 165 ± 61.3 min in the CC and NT groups, respectively, and there was a significant difference between the two groups (P < 0.05). There were no significant differences in complete resection rate, perforation rate and bleeding rate between the two groups. The cross-counter technique shortened the treatment time in colorectal ESD without any complication.


Redescription of Pseudopoda taibaischana (Araneae, Sparassidae), with the first description of the female.
Pseudopoda taibaischana Jäger, 2001 (Sparassidae) is redescribed based on new material from the type locality in Taibaishan Nation Forest Park of Shaanxi Province, China. The female is described and illustrated for the first time, and a redescription is provided for the male.


[The development of adaptive body reactions after intensive physical loading].
30 min and 3 hours after intensive exercise (swimming) rats developed both microcirculatory compensatory-adaptive changes in the myocardium, cerebral cortex, liver and destruction at the level of membrane connective tissue structures especially manifest in the myocardium early after the exercise.


Singleness of action in the interactions of feeding with other behaviors in Hermissenda crassicornis.
Singleness of action in the interactions of feeding behavior with other behaviors was studied in Hermissenda crassicornis. In Experiment 1 withdrawal of the oral veil from a tactile stimulus was inhibited during feeding elicited by application of a mussel homogenate to hungry animals. Rolling-over behavior was also inhibited during feeding. When animals were satiated, thereby abolishing the feeding response to mussel homogenate, withdrawal occurred in the presence of the food stimulus; however, rolling-over behavior was still inhibited. In Experiments 2 and 3 it was demonstrated that spontaneous locomotion was also inhibited in hungry animals by food stimuli; however, satiated animals ignored the food stimulus and continued to locomote. Both biting behavior and the suppressive effect of food stimuli on locomotion were also observed in dissected anterior ends of Hermissenda, suggesting that the mechanisms underlying the interaction of feeding with other behaviors may be accessible to study in the nervous system of reduced preparations.


Stereotactically guided radiosurgery using the linear accelerator.
Leksell initiated the concept of stereotactic radiosurgery in 1951. This last decade has seen a rapid proliferation in the development of the methodology which is certainly related in part to the simultaneous growth of high-resolution neuro-imaging techniques. By focusing the beams of 201 hemispherically arrayed cobalt 60 sources, the gamma-knife delivers a high dose of radiation to a small target. Another possibility proposed by several authors is the bragg peak cyclotron-generated irradiation with accelerated protons or helium ions. In Lille, since 1988, we have chosen to develop stereotactic radiosurgery, according to the system of Betti, by the association of Talairach's stereotactic methodology and external single-dose encephalic irradiation with high energy X-rays, delivered by means of a linear accelerator. The major indication for the use of this method is an arteriovenous malformation. Stereotactic radiosurgery may be proposed alone or in combination with surgery and embolisation. It has been shown to be a potentially effective treatment and an attractive alternative in carefully selected patients with intracranial tumours: slow-growing, well limited, deep-seated tumours, such as some gliomas, acoustic neurinomas, skull base meningiomas, pituitary adenomas. This treatment is also used to deliver a focal boost of radiation to previously administered fractionated radiotherapy in patients with small gliomas and solitary brain metastases.


Mito-SiPE is a sequence-independent and PCR-free mtDNA enrichment method for accurate ultra-deep mitochondrial sequencing.
The analysis of somatic variation in the mitochondrial genome requires deep sequencing of mitochondrial DNA. This is ordinarily achieved by selective enrichment methods, such as PCR amplification or probe hybridization. These methods can introduce bias and are prone to contamination by nuclear-mitochondrial sequences (NUMTs), elements that can introduce artefacts into heteroplasmy analysis. We isolated intact mitochondria using differential centrifugation and alkaline lysis and subjected purified mitochondrial DNA to a sequence-independent and PCR-free method to obtain ultra-deep (>80,000X) sequencing coverage of the mitochondrial genome. This methodology avoids false-heteroplasmy calls that occur when long-range PCR amplification is used for mitochondrial DNA enrichment. Previously published methods employing mitochondrial DNA purification did not measure mitochondrial DNA enrichment or utilise high coverage short-read sequencing. Here, we describe a protocol that yields mitochondrial DNA and have quantified the increased level of mitochondrial DNA post-enrichment in 7 different mouse tissues. This method will enable researchers to identify changes in low frequency heteroplasmy without introducing PCR biases or NUMT contamination that are incorrectly identified as heteroplasmy when long-range PCR is used.


Ascorbate in the corneal epithelium of diurnal and nocturnal species.
To compare the amount of ascorbic acid in the corneal epithelium of various species to unveil possible differences between diurnal and nocturnal mammals. Ascorbic acid was determined by high-performance liquid chromatography, using an LC-10 system (Shimadzu, Kyoto, Japan). Diurnal animals show a higher ascorbate concentration in the corneal epithelium than nocturnal animals. Ascorbate concentration is higher in the corneal epithelium than in the matching aqueous humor in diurnal and nocturnal species. The highest ascorbate concentration is found in the corneal epithelium of the reindeer. Ascorbate level in the corneal epithelium seems to vary in accordance with ambient radiation exposure of the respective species, just as in the aqueous humor. Both phenomena are regarded as environmental adaptations, and the ascorbic acid is suggested as protecting against photokeratitis and as acting as an ultraviolet filter for internal eye structures.


Isolated uvular angioedema associated with ACE inhibitor use.
Angioedema is a well-known complication of medical therapy with angiotensin-converting enzyme (ACE) inhibitors. Isolated uvular angioedema, a rare presentation of angioedema, in a patient taking lisinopril (Zestril) is described in this case report. Management of uvular edema is also reviewed.


FGFR4 regulates tumor subtype differentiation in luminal breast cancer and metastatic disease.
Mechanisms driving tumor progression from less aggressive subtypes to more aggressive states represent key targets for therapy. We identified a subset of luminal A primary breast tumors that give rise to HER2-enriched (HER2E) subtype metastases, but remain clinically HER2 negative (cHER2-). By testing the unique genetic and transcriptomic features of these cases, we developed the hypothesis that FGFR4 likely participates in this subtype switching. To evaluate this, we developed 2 FGFR4 genomic signatures using a patient-derived xenograft (PDX) model treated with an FGFR4 inhibitor, which inhibited PDX growth in vivo. Bulk tumor gene expression analysis and single-cell RNA sequencing demonstrated that the inhibition of FGFR4 signaling caused molecular switching. In the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) breast cancer cohort, FGFR4-induced and FGFR4-repressed signatures each predicted overall survival. Additionally, the FGFR4-induced signature was an independent prognostic factor beyond subtype and stage. Supervised analysis of 77 primary tumors with paired metastases revealed that the FGFR4-induced signature was significantly higher in luminal/ER+ tumor metastases compared with their primaries. Finally, multivariate analysis demonstrated that the FGFR4-induced signature also predicted site-specific metastasis for lung, liver, and brain, but not for bone or lymph nodes. These data identify a link between FGFR4-regulated genes and metastasis, suggesting treatment options for FGFR4-positive patients, whose high expression is not caused by mutation or amplification.


The arterial sling operation: one-year follow-up.
Coronary artery bypass graft surgery with total arterial revascularization, particularly the use of bilateral in situ internal thoracic arteries, is considered an improved treatment of patients with ischemic heart disease. The sling operation connects the internal thoracic arteries with the radial artery, creating an arterial arcade with double inlet of blood to the peripheral vascular bed. In this paper we present 1-year follow up of angiographic and clinical results of the arterial sling operation. The arterial sling operation was performed in 28 patients in the period from October 2000 to September 2001, and all patients were offered an angiographical and clinical examination 1 year postoperatively. All angiograms were systematically reviewed by an interventional cardiologist and a cardiac surgeon. Twenty-three patients participated in the 1-year angiographic follow up. Of these 3 patients had a fully open arterial sling, 15 patients had stenosis or occlusion of one segment, and 5 patients had occlusion or stenosis of 2 segments of the radial artery. Eight of the total 93 peripheral anastomoses were occluded. The 1-year graft patency rate was 91.4%. The arterial sling operation is safe and the one year patency rate is high. Although one or two segments of the arterial sling may degenerate due to competitive blood flow, this does not affect blood flow in the vascular bed in patients without disease progression. However, arterial revascularization should be performed in a way to minimize competitive flow.


Fresh frozen plasma in the pediatric pump prime: a prospective, randomized trial.
The aim of this study was to determine whether the use of fresh frozen plasma (FFP) in the infant pump prime can avoid dilution of fibrinogen, decrease the need for blood product transfusion after bypass, and decrease exposure to donor blood products. Twenty infants weighing less than 8 kg were prospectively randomized to receive either 1 U of FFP (10 patients) or no FFP (10 patients) in the pump prime. Mean age (4.2 +/- 2.8 months), weight (4.3 +/- 1.1 kg), total prime volume (641 +/- 96 ml), cardiopulmonary bypass time, cross-clamp time, lowest temperature on bypass, and preoperative coagulation parameters did not differ between the two groups. At the end of bypass, the mean fibrinogen level was significantly higher in the FFP than the no FFP group (123 +/- 20 versus 58 +/- 17 mg/dL; p < 0.0001), whereas the mean platelet count did not differ (60 +/- 25 versus 52 +/- 26 K/mm(3); p = 0.5). Patients in the FFP group received significantly fewer units of cryoprecipitate (0.4 +/- 0.8 versus 2.0 +/- 0.9 U/patient; p < 0.001), and had a mean total donor exposure of 4.1 +/- 1.5 U/patient versus 5.4 +/- 1.4 U/patient in the no FFP group (p = 0.06). The mean chest tube output over the first 24 hours did not differ between groups. The use of FFP in the pump prime significantly limited dilutional hypofibrinogenemia, decreased the transfusion of cryoprecipitate after bypass, and tended to decrease the overall mean patient exposure to blood products.


Monitoring of continuous subcutaneous insulin infusion treatment in Portugal and its implications for diabetes management.
Intensive insulin therapy in the treatment of type 1 diabetes can, in place of multiple daily injections of subcutaneous insulin (MDI), be performed with continuous subcutaneous insulin infusion (CSII) systems. This method allows for better glycemic control and thus reduces the risk of complications of the disease. The aim of this study was to evaluate the results of treatment with CSII in Portugal. A retrospective analysis of the records on the national CSII platform was carried out between January 2010 and August 2021. All the registered patients are followed in certified CSII treatment centers in Portugal. Of the 7135 registered patients, 3807 were excluded due to absence of monitoring data. The reasons for treatment were analyzed and a comparison was made between patients with and without CSII. The statistical significance considered was α < 0.05. A total of 3328 patients were included in the study, 1136 under MDI and 2192 under CSII. The main reasons for CSII use were marked glycemic variability (25%) and HbA1c greater than 7% (23%). Patients under CSII had a lower HbA1c (7.7 ± 1.0% vs. 8.0 ± 1.5%, p < 0.001), as well as a lower frequency of episodes of severe hypoglycemia (1.4 vs. 3.3 per 100 patient-years, p < 0.001), and ketoacidosis (1 vs. 2.4 per 100 patient-years, p < 0.001). The present analysis validates the advantage of using CSII in metabolic control and reduction of acute complications of type 1 diabetes, both severe hypoglycemia and ketoacidosis, in the Portuguese population. CSII therapy is classically associated with an increased risk of ketoacidosis; however, in experienced centers and adequate patient education, the opposite is found.


War trauma and strategies for coping with stress among Ukrainian refugees staying in Poland.
The Russian military aggression against Ukraine resulted in a humanitarian crisis. There was a mass exodus of war refugees. More than 17 million people have left Ukraine since the war broke out. The refugees who came to Poland and other countries have experienced war trauma. The study aims to assess mental health of Ukrainian war refugees in Poland. At the time of the study, that is, in April and May 2022, between 1,5 million and 2 million Ukrainian refugees were staying in Poland. They were mainly young women with their children. The CAWI (Computer-Assisted Web Interview) technique was used in the study. The research sample was selected using purposive sampling. The invitation to take part in the survey was posted on social media for Ukrainians in Poland, and also sent to the participants of a Polish as a Foreign Language course. The study utilizes the RHS-15 and a nominal scale measuring the strategies for coping with stress. The research sample consists of 737 respondents. The results of the screening tests indicate that depression, anxiety disorders and PTSD may be observed among 73% of respondents, whereas 66% of the respondents display psychological distress. The analyses have shown that higher levels of mental health disorders were observed among women and refugees who do not speak Polish. Younger respondents experienced a higher psychological distress. The results of the study also indicate that the refugees more often implemented problem-focused strategies. The analysis has shown that the respondents who followed active strategies scored the lowest on RHS-15. The emotion-focused strategies, such as praying, diverting attention by becoming involved in different activities or taking sedatives were not effective. The highest levels of disorders were present among the refugees who indicated resignation. The collected observations indicate that the main problem which might hinder their adaptation could be mental health issues, which in turn impact the general deterioration of health and the quality of life.


Total parenteral nutrition in patients following pancreaticoduodenectomy: lessons from 1184 patients.
Total parenteral nutrition (TPN) has historically been used conservatively in the management of patients after pancreaticoduodenectomy (PD). Herein, we evaluate the indications for and outcomes associated with TPN use in a high-volume pancreatic surgery center. We retrospectively queried our institution's pancreatic surgery database for patients who received TPN after PD from 2006 through 2015. Of 1184 patients who underwent PD, 232 (19.6%) received TPN perioperatively. The most common indications for TPN were delayed gastric emptying (DGE, n = 171, 73.7%), pancreatic fistula (n = 102, 44%), and generalized malnutrition (n = 25, 10.8%). The median day of TPN initiation was postoperative day 4 (range: -31 to 22), with a median usage of 9 days (range: 1-115). Forty-four (19%) patients received short-course TPN (≤3 days), primarily those diagnosed with isolated grade A DGE without associated complications (P = 0.0003). Multivariate analysis suggests the presence of deep surgical site infection (odds ratio: 3.09, [1.16-5.06], P = 0.018) or pancreatic fistula (odds ratio: 2.57, [1.03-6.41], P = 0.043) at the time of DGE presentation as predictive of long-term TPN requirement. Hyperglycemia (34.5%) was the most common complication resulting from TPN use, whereas central line-associated bloodstream infections (2.6%) were rare. Readmissions (35.3% TPN cohort; 15% historical institutional rate) were most commonly due to poor oral intake (26.8%). The 30-day mortality rate in the overall TPN cohort was 3.4% (0.8% historical institutional rate). TPN is a critical and safe adjunct for patients who develop PD-associated complications; however, it may be of limited utility for patients with isolated DGE.


Density weighted turbo spin echo imaging.
To optimize the spatial response function (SRF) while maintaining optimal signal to noise ratio (SNR) in T2 weighted turbo spin echo (TSE) imaging by prospective density weighting. Density weighting optimizes the SRF by sampling the k-space with variable density without the need of retrospective filtering, which would typically result in nonoptimal SNR. For TSE, the T2 decay needs to be considered when calculating an optimized sampling pattern. Simulations were carried out and T2 weighted in vivo TSE measurements were performed on a 3 Tesla MRI system. To evaluate the SNR, reversed centric density weighted and retrospectively filtered Cartesian acquisitions with identical measurement parameters and SRFs were compared with TE(eff) = 90 ms and a density weighted k-space sampling optimized to yield a Kaiser function for SRF side lobe suppression for white matter. Density weighting of a reversed centric reordering scheme resulted in an SNR increase of (43 ± 13)% compared with the Cartesian acquisition with retrospective filtering while maintaining comparable contrast behavior. Density weighting is applicable to TSE imaging and results in significantly increased SNR. The gain can be used to shorten the measurement time, which suggests applying density weighting in both time and SNR constrained MRI.


Emotional Experiences of Skin Markings Among Patients Undergoing Radiotherapy and Related Factors: A Questionnaire-Based Cross-Sectional Study.
Patients undergoing radiotherapy often have their skin marked. Previous studies on skin markings examined the durability and physical effects of the markings, but no study has focused on patients' emotional experiences toward the markings. This study aimed to clarify how patients undergoing radiotherapy feel about skin markings, as well as factors that affect patients' emotional experiences. We conducted a cross-sectional study using a self-administered questionnaire and medical records. Participants were patients aged ≥20 years undergoing cancer radiotherapy at a designated cancer care hospital. The primary outcome was the level of uncomfortable emotions toward skin markings, and the secondary outcome was the level of favorable ratings on skin markings. To examine factors related to uncomfortable emotions, ordinal logistic regression analysis was performed. Questionnaire forms were distributed to 153 patients, and responses were collected from 132 (86%). Among 108 patients included in the analysis, 56% (59/105, excluding 3 who did not answer this question) responded that they were uncomfortable with skin markings. The proportion of patients who favorably rated skin markings was 63% (59/93, excluding 15 who did not answer this question). No factors were significantly associated with the primary outcome. Many patients accepted skin markings with resignation, as they understood the necessity of the markings in their treatment. Medical staff should understand the emotional experiences of patients toward skin markings and take sufficient care to ensure that they are provided with explanations, including the impact of skin markings on their daily lives, as well as a sense of security that treatment is being performed in a precise manner.


Neuronal cGMP kinase I is essential for stimulation of duodenal bicarbonate secretion by luminal acid.
Brief contact of the duodenal mucosa with luminal acid elicits a long-lasting bicarbonate (HCO(3)(-)) secretory response, which is believed to be the primary protective mechanism against mucosal damage. Here, we show that cGMP-dependent protein kinase type I-knockout (cGKI(-/-)) mice are unable to respond to a physiological H(+) stimulus with a HCO(3)(-) secretory response and spontaneously develop duodenal ulcerations. Smooth muscle-selective cGKI knock-in rescued the motility disturbance but not the defective HCO(3)(-) secretion. Proton-induced HCO(3)(-) secretion was not attenuated by selective inactivation of the cGKI gene in interstitial cells of Cajal or in enterocytes, but was abolished by inactivation of cGKI in neurons (ncGKI(-/-)). cGKI was expressed in the brainstem nucleus tractus solitarius that connects the afferent with the efferent N. vagus. Accordingly, truncation of the subdiaphragmal N. vagus significantly diminished proton-induced HCO(3)(-) secretion in wild-type mice, whereas stimulation of the subdiaphragmal N. vagus elicited a similar HCO(3)(-) secretory response in cGKI(-/-), ncGKI(-/-) and wild-type mice. These findings show that protection of the duodenum from acid injury requires neuronal cGKI.


Mammalian tumor-like organs. 2. Mammalian adipose has many tumor features and obesity is a tumor-like process.
In previous publications, the author developed the theory of carcino-evo-devo, which predicts that evolutionarily novel organs should recapitulate some features of tumors in their development. Mammalian adipose is currently recognized as a multi-depot metabolic and endocrine organ consisting of several adipose tissues. Although lipid-storing cells and proteins are ancient, the adipose organ as a whole is evolutionarily novel to mammals. The adipose expansion has remarkable similarities with the growth of solid tumors. These similarities are the following: (1) The capability to unlimited expansion; (2) Reversible plasticity; (3) Induction of angiogenesis; (4) Chronic inflammation; (5) Remodeling and disfunction; (6) Systemic influence on the organism; (7) Hormone production; (8) Production of miRNAs that influence other tissues; (9) Immunosuppression; (10) DNA damage and resistance to apoptosis; (11) Destructive infiltration in other organs and tissues. These similarities include the majority of "hallmarks of cancer". In addition, lipomas are the most frequent soft tissue tumors, and similar drugs may be used for the treatment of obesity and cancer by preventing infiltration. This raises the possibility that obesity, at least in part, may represent an oncological problem. The existing similarities between adipose and tumors suggest the possible evolutionary origin of mammalian adipose from some ancestral benign mesenchymal hereditary tumors. Indeed, using a transgenic inducible zebrafish tumor model, we described many genes, which originated in fish and were expressed in fish tumors. Their human orthologs LEP, NOTCH1, SPRY1, PPARG, ID2, and CIDEA acquired functions connected with the adipose organ. They are also involved in tumor development in humans. If the hypothesis of the evolutionary origin of the adipose organ from the ancestral hereditary tumor is correct, it may open new opportunities to resolve the oncological problem and the problem of the obesity epidemic. New interventions targeting LEP, NOTCH1, SPRY1, PPARG, ID2, and CIDEA gene network, in addition to what already is going on, can be designed for treatment and prevention of both obesity and tumors.


Serotype variation of group A rotaviruses over nine winter epidemics in southeastern New England.
By the use of enzyme immunoassay and RNA electrophoresis, rotavirus serotyping was performed with stool specimens from 605 children. Serotypes 1, 2, 3, and 4 accounted for 63, 9, 9, and 19% of the cases, respectively, with considerable yearly variation. An average of three serotypes cocirculated each year.


Transurethral balloon divulsion of prostate.
Benign prostatic hypertrophy (BPH) is the most common cause of urinary outflow obstruction. Transurethral resection of the prostate (TURP) is the preferred treatment for symptomatic BPH and is considered the gold standard of treatment. Balloon dilatation of the prostate (TUBD), besides some criticism, represents a nonoperative treatment alternative for treatment of symptomatic BPH which is simple and safe. We describe the technique of TUBD, balloon technology, as well as advantages and disadvantages of balloon dilatation.


Ethics and science: educating the public.
This article looks at the public debate which took place in the first half of the twentieth century and has repercussions to the present day. It was about the ethical stance of scientists, and how science should be organized. In particular, it examines the positions taken by Professor F. Soddy, F.R.S. and Nobel Laureate, who stressed the responsibility of scientists for the uses made of their research, Professor Michael Polanyi, F.R.S., who emphasised the obligation of scientists to the truth and the essential role of morality in the organization of science, and Professor J.D. Bernal, F.R.S., who insisted that science was practiced for utilitarian reasons and should be consciously developed for the good of society.


IL-1β Is Involved with the Generation of Pain in Experimental Autoimmune Encephalomyelitis.
Pain is one of the main symptoms of multiple sclerosis, a demyelinating disease of the central nervous system that affects millions of people worldwide. The experimental autoimmune encephalomyelitis (EAE) is considered an experimental model of multiple sclerosis, and besides motor weakness, hypernociception is one of the clinical signs of animals with EAE. In this study, we investigated the influence of some cytokines in the generation of the hypernociceptive response in a mouse model of EAE using MOG35-55. We measured some cytokines in the dorsal root ganglia (DRG), an important anatomical structure involved in pain. We found increased levels of the cytokines TNF-α, IL-1β, and Kc in DRGs of animals with EAE. We used the antibody IL-1ra to antagonize the effects of IL-1β, and animals presented a decrease in the hypernociceptive response. Thus, our results suggest that hypernociception in this experimental model of EAE may be a consequence of the increase in some cytokines in DRGs, especially IL-1β.


Influenza A(H1N1)pdm09 virus exhibiting reduced susceptibility to baloxavir due to a PA E23K substitution detected from a child without baloxavir treatment.
Human-to-human transmission of PA I38 mutant influenza A(H3N2) viruses with reduced baloxavir susceptibility has been reported in Japan. In December 2019, we detected a PA E23K mutant A(H1N1)pdm09 virus from a child without baloxavir treatment. The PA E23K mutant virus exhibited reduced baloxavir susceptibility but remained susceptible to neuraminidase inhibitors. Epidemiological data suggest possible transmission of this PA E23K mutant virus among humans, although its growth capability relative to that of the wild-type virus was reduced. Therefore, baloxavir susceptibility monitoring of influenza viruses is essential.


Update on pharmacotherapy for dry eye.
This review provides an overview of pharmacologic treatments for dry eye disease (DED), with a focus on newer developments. Along with the existing treatments, there are several new pharmacologic treatments available and being developed for DED. There are many currently available options for treatment of DED, and ongoing research and development to expand potential treatments for patients with DED.


Synthesis, Structure of Nitrogen-Containing Phosphinogold(I) Ferrocenes. In vitro Activity against Bladder and Colon Carcinoma Cell Lines.
The gold salt [(tht)AuCl] was reacted with [1-N,N-dimethylaminométhyl-2-diphenylphosphino]ferrocene (1) forming the bimetallic derivative 4. The reaction of methyl iodide and tetramethylammonium bromide on the chloride 4 produced the ammonium salt 5 and the bromide 6 respectively. New aminophosphines 2 and 3, which represent two of the rare phosphorylated metallocenes containing P(III)-N bond have also been coordinated to gold(I) to form 7 and 8. The presence of the ethoxy group in 7 provides evidence for the lability of one nitrogen-phosphorus bond. The X-ray structure of compounds 4 and 7 have been established. Both crystallize in space group P2(1)/c, monoclinic, with a = 11.095(2) A, b = 12.030(3) A, c = 17.763(4) A, beta= 94.02(2) composite function, Z = 4 for 4 and a = 14.863(3) A, b = 8.036(5)A, c = 18.062(5)A, beta =101.64(1) degrees , Z = 4 for 7. (197)Au Mössbauer data are in good agreement with those for other linear P-Au-Cl containing complexes. The compounds were evaluated for in vitro anti-tumour activity against two human tumours. Differential cytotoxicity was observed with activity comparable to cisplatin, with the exception of one compound which was significantly more cytotoxic.


Vincristine and vinblastine lower plasma cholesterol concentrations in rhesus monkeys.
3-4 days after a single clinical dose of vincristine or vinblastine in rhesus monkeys there was a marked decrease in plasma low-density lipoprotein cholesterol concentrations. There was also a concomitant increase in plasma triacylglycerol concentrations. Plasma lipid levels returned to normal concentrations within 7-10 days after injection. Plasma high-density lipoprotein cholesterol concentrations were unaltered by the drugs. Electron micrographs of the hepatocytes from monkeys treated with vincristine or vinblastine showed an accumulation of glycogen particles and proliferation of smooth endoplasmic reticulum, which was accompanied by an increase in the number of lipoprotein-containing vesicles. These results indicate that vincristine and vinblastine alter plasma cholesterol and triacylglycerol concentrations in part by interfering with hepatic lipid and lipoprotein metabolism. These studies further suggest the possibility that other less cytotoxic alkaloids from Catharanthus species with clinically useful hypocholesterolemic activity may be discovered.


Phenolic glycolipid-1 from M. leprae inhibits oxygen free radical production by human mononuclear cells.
We studied the effect of PGL1, a phenolic glycolipid unique to Mycobacterium leprae, on the activation of the phagocyte oxidative respiratory burst, by measuring the chemiluminescence (CL) generated by normal mononuclear cells. PGL1 induced a decrease in oxygen free radical production stimulated by mycobacteria (M. leprae, BCG and M. kansasii) or by phorbol myristate acetate, but did not prevent the binding or ingestion of fluorescein-conjugated mycobacteria. In contrast, mycoside A from M. kansasii, a structurally related compound, did not alter the CL response. In addition, treatment of M. leprae with anti-PGL1 antibodies failed to restore the response to this microorganism. PGL1 could act as an oxygen species scavenger and protect M. leprae from killing by toxic oxygen metabolites.


Cholesterol and ORP1L-mediated ER contact sites control autophagosome transport and fusion with the endocytic pathway.
Autophagy is the main homeostatic pathway guiding cytosolic materials for degradation by the lysosome. Maturation of autophagosomes requires their transport towards the perinuclear region of the cell, with key factors underlying both processes still poorly understood. Here we show that transport and positioning of late autophagosomes depends on cholesterol by way of the cholesterol-sensing Rab7 effector ORP1L. ORP1L localizes to late autophagosomes and-under low-cholesterol conditions-contacts the ER protein VAP-A, forming ER-autophagosome contact sites, which prevent minus-end transport by the Rab7-RILP-dynein complex. ORP1L-mediated contact sites also inhibit localization of PLEKHM1 to Rab7. PLEKHM1, together with RILP, then recruits the homotypic fusion and vacuole protein-sorting (HOPS) complex for fusion of autophagosomes with late endosomes and lysosomes. Thus, ORP1L, via its liganding by lipids and the formation of contacts between autophagic vacuoles and the ER, governs the last steps in autophagy that lead to the lysosomal degradation of cytosolic material.


Two new species of the spider genus Sinamma Lin amp; Li, 2014 (Araneae, Tetrablemmidae) from Guangdong Province, China.
Two new species of the genus Sinamma Lin Li, 2014, Sinamma quadrata Tong Li, sp. nov. (male, female) and Sinamma yingae Tong Li, sp. nov. (male, female) are described from Guangdong, China. The geographic distribution of the genus is updated and a key to all known species is provided.


Disorders of the lymphatic homing and MIF production by the lymphocytes of thymus, spleen and lymph nodes after liver injury caused by portocaval shunt in rats.
This paper presents the quantitative changes and disorders in migratory inhibition factor (MIF) production by thymus, lymph node and spleen cells after liver injury provoked by the porto-caval shunt (PCS) in rats. The great depopulation of the lymphatic organs, particularly the thymus, was demonstrated. The reduction of MIF generation after PCS was also noticed. The severe liver injury reflected by high activity of GOT and GPT was observed on the second day after surgical procedure. Our investigations bring into light the multifold interrelationships between the functionally efficient liver and lymphatic organs in rat.


Refined mapping of the gene for thiamine-responsive megaloblastic anemia syndrome and evidence for genetic homogeneity.
Thiamine-responsive megaloblastic anemia (TRMA, also known as Rogers syndrome, OMIM 249270) is a rare autosomal recessive disorder characterized by a triad of megaloblastic anemia, diabetes mellitus, and sensorineural deafness. Patients respond, to varying degrees, to treatment with megadoses of thiamine. We have recently shown genetic linkage of the TRMA gene to a 16-centimorgan (cM) region on 1q23.2-1q23.3 based on the analysis of four large, inbred families of Alaskan, Italian, and Israeli-Arab origin. Here we narrow the TRMA interval down to 4 cM based on genetic recombination, homozygosity mapping, and linkage disequilibrium (highest LOD score of 12.5 at D1S2799, at a recombination fraction of 0). We provide further evidence that the TRMA gene is located in this region and confirm the homogeneity of the disease. In this analysis, we genotyped seven additional families of diverse ethnic origin (Pakistani, Indian, Italian, Brazilian, and Japanese), and analyzed additional markers in two previously reported families showing evidence of linkage disequilibrium in a large area of their haplotypes. The multi-system manifestations of TRMA suggest that thiamine has a pivotal role in a multiplicity of physiological processes. Mapping the TRMA gene and understanding the molecular basis of the disease might, thus, shed light on the role of thiamine in common disorders such as deafness, anemia, and diabetes.


Aspirin and Nonsteroidal Antiinflammatory Drugs Hypersensitivity and Management.
Aspirin and nonsteroidal antiinflammatory drugs (NSAIDs) are widely used in the United States and throughout the world for a variety of indications. Several unique hypersensitivity syndromes exist to this class of medications, making them one of the common reasons for consultation to the allergist. The lack of any laboratory-based diagnostic studies to assist in identifying the culprits in these reactions make evaluation of aspirin and NSAID hypersensitivity challenging. Identifying patients appropriate for oral challenge and/or desensitization protocols is the standard pragmatic approach to this issue when it arises.


Underdiagnosed veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) as a major cause of multi-organ failure in acute leukemia transplant patients: an analysis from the EBMT Acute Leukemia Working Party.
Allogeneic hematopoietic cell transplantation (alloHCT) is a complex, potentially fatal therapy featuring a myriad of complications. Triggering event(s) of such complications vary significantly, but often a so-called "multi-organ failure" (MOF) is reported as the leading cause of death. The identification of the exact trigger of MOF is critical towards early and disease-specific intervention to improve outcome. We examined data from 202 alloHCT patients reported to have died of MOF from the EBMT registry aiming to determine their exact cause of death focusing on veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) due to its life-threatening, often difficult to capture yet preventable nature. We identified a total of 70 patients (35%) for whom VOD/SOS could be considered as trigger for MOF and leading cause of death, among which 48 (69%) were previously undiagnosed. Multivariate analysis highlighted history of hepatic comorbidity or gentuzumab use and disease status beyond CR1 as the only significant factors predictive of VOD/SOS incidence (OR = 6.6; p = 0.001 and OR = 3.3; p = 0.004 respectively). VOD/SOS-related MOF was widely under-reported, accounting for 27% of deaths attributed to MOF of unknown origin without a previous VOD/SOS diagnosis. Our results suggest most missed cases developed late VOD/SOS beyond 21 days post-alloHCT, highlighting the importance of the newly revised EBMT criteria.


Individuals' perceptions of social support from family and friends are associated with lower risk of sleep complaints and short sleep duration.
To examine whether individuals' perceptions of social support (SS) from partners, other family members, and friends are associated with risk of sleep complaints and short sleep duration. A cross-sectional and prospective study with 1,688 community dwelling adults from the Retirement and Sleep Trajectories study. Four annual, self-administered questionnaires were mailed to participants in the year 2010-2014. Self-reports of individuals' perceptions of SS were obtained at the baseline survey. Sleep quality and duration were self-reported on each of the four surveys over the follow-up. Associations were examined with mixed-effect models, controlling for confounders. In fully adjusted analyses, compared with those reporting low SS from their partner, the risk of reporting more than 1 sleep symptom was significantly lower among those with intermediate (relative risk, RR = 0.68; 95% confidence interval, CI = 0.53-0.87) and high SS (RR = 0.61; 95% CI=0.48-0.77). Similarly, relative to those with low SS, those reporting high SS from family (RR = 0.74; 95% CI = 0.57-0.94) and friends (RR = 0.73; 95% CI = 0.58-0.92) had lower risk of having more than 1 sleep symptom. Compared with those with low, intermediate (RR = 0.70; 95% CI = 0.52-0.96), and high SS (RR = 0.63; 95% CI = 0.48-0.84) from partners, intermediate (RR = 0.76; 95% CI = 0.59-0.97) and high SS (RR = 0.69; 95% CI = 0.51-0.92) from family and high SS (RR = 0.74; 95% CI = 0.56-0.99) from friends were associated with lower risk of short sleep (≤6 h). The perception of higher SS from relatives and friends is independently associated with lower risk of poor sleep quality and short sleep duration. Future research and intervention studies should test whether strengthening social relationships can positively effect sleep health.


Five-year experience with valve sparing surgery for aortic root aneurysms.
The aim of this study was to analyze the mid-term results of aortic root reconstruction. Between September 1995 and March 2001, 32 patients (25 males, 7 females, median age 58 +/- 21 years) underwent aortic root reconstruction as described by T. David. Indications for operation were aortic insufficiency with ascending aortic aneurysm in 27 patients, and acute aortic dissection (Stanford type A) in 5 patients. In all patients the native valve was preserved and suspended inside a tubular prosthesis with reimplantation of the coronary arteries. In 10 patients the classic reconstruction technique was modified by shaping a "Neosinus." There was one perioperative death due to myocardial infarction. Two patients suffered a stroke. 26 patients were followed up 12 months postoperatively. 22 out of 26 patients were in NYHA functional class I, 2 patients in class II and the remaining 2 in class III. Three patients died in the postoperative period. Six patients had trivial AR, 4 mild and 1 moderate regurgitation. There were no thromboembolic events during follow up. The mean transvalvular gradient was 3.5 +/- 2.2 mmHg. Compared to a normal cohort of patients (n = 20), resuspended aortic valves opened (26.4 +/- 5.8 vs. 61.3 +/- 22.1 cm/sec, p < 0.0001) and closed (22.8+/- 6.9 vs. 57.9 +/- 22.3) at a higher speeds and also showed shorter opening (0.053 +/- 0.12 vs. 0.023 +/- 0.09 sec, p < 0.0001) and closing times (0.051 +/- 0.07 vs. 0.23 +/- 0.07 cm/sec) of the aortic leaflets. Aortic valve reimplantation is a reliable technique able to reduce long term complications when compared to conventional composite graft replacement of the aortic root. Altered leaflet opening and closing dynamics do not impair midterm durability.


Selective sensing of catechol based on a fluorescent nanozyme with catechol oxidase activity.
Nanozymes, an unusual category of nanomaterials possessing enzymatic properties, and have generated considerable interest regarding their application feasibilities on several important fronts. In the present work, an innovative sensing device for catechol was established ground on a fluorescent nanozyme (Cu-BDC-NH2) that exhibited catechol oxidase activity. The fluorescent nanozyme combines both functions of catechol recognition and response signal output, and can realize the sensing of catechol without the addition of other chromogenic agents. In the existence of Cu-BDC-NH2, catechol can be oxidized efficiently to produce quinones or polymers with strong electron absorption capacity, which immediately results in efficient fluorescence quenching of Cu-BDC-NH2. However, other common phenolic compounds, such as phenol, the other two diphenols (hydroquinone and resorcinol), phloroglucinol, and chlorophenol, do not result in efficient fluorescence quenching of Cu-BDC-NH2. The method shows a nice linear relationship between catechol concentration prep the fluorescence intensity of Cu-BDC-NH2 in the scope of 0-10 μM, with a detection limit of 0.997 μM. The detection of catechol in actual water samples has also achieved the satisfactory consequences, which provides a new strategy for the convenient and selective detection of catechol.


A cross-sectional evaluation of adiponectin plasma levels in patients with schizophrenia and schizoaffective disorder.
In recent years, several studies showed increased rates of hyperglycaemia, diabetes, dyslipidemia, metabolic syndrome as well as cardiovascular disease in schizophrenic patients. The underlying mechanism, however, is poorly understood. Adiponectin is a recently identified adipocyte-derived protein, with low adiponectin levels being associated with metabolic abnormalities such as obesity, insulin resistance and type 2 diabetes. Fasting adiponectin levels were assessed in a cross-sectional sample of 386 patients with schizophrenia or schizoaffective disorder. All patients were on monotherapy of second-generation antipsychotics (SGA) and underwent an extensive metabolic screening including an oral glucose tolerance test (OGTT). Adiponectin plasma levels were inversely correlated with BMI, and differed significantly between patients with normal weight, overweight or obesity (p<0.05). Patients who met criteria for the metabolic syndrome, according to adapted National Cholesterol Educational Program - Adult Treatment Panel criteria (NCEP-ATP III) (29.3%), had significantly lower adiponectin levels than patients not meeting metabolic syndrome criteria (p<0.0001). Patients without glucose abnormalities (78%) had significantly higher adiponectin levels than patients with diabetes (5.7%) (p<0.05). After controlling for components of metabolic syndrome and sex, antipsychotic medication independently influenced adiponectin levels (p<0.0001), with the lowest mean levels in patients on clozapine and olanzapine. Adiponectin levels in schizophrenic patients mirror what is observed in the general population, with the lowest levels in the most metabolically comprised subjects. However, antipsychotic medication may also influence adiponectin regulation independently, a finding that should be confirmed in longitudinal studies.


Hyperventilation stimulates the release of prostaglandin I2 and E2 from lung in humans.
It has been reported that hyperventilation (HV) increases the release of vasodilative prostaglandins (PGs) from animal lungs. However, it has not yet been clarified whether or not the results obtained from animal experiments are applicable to humans. To confirm this point, we performed this study. Healthy male volunteers, aged 22-28 years, were divided into two groups. Group I (n = 11) breathed room air and showed respiratory alkalosis. Group II (n = 11) breathed room air containing 5% CO2 and maintained normal arterial blood pH. Each subject hyperventilated voluntarily and vigorously for 10 min. The mean values of respiratory rates, tidal volumes and minute volumes during HV were 42.1 +/- 6.2 breaths/min, 1390 +/- 280 ml and 58.5 +/- 15.2 l/min, respectively. Arterial and venous blood samples were drawn simultaneously before and after HV from brachial artery and medial cubital vein, respectively. Plasma 6-keto PGF1 alpha, a metabolite of PGI2, and PGE2 were measured by radioimmunoassay (RIA). After HV, concentrations of 6-keto PG F1 alpha and PGE2 in both arterial and venous blood were increased significantly. There were no significant differences in the levels of 6-keto PGF1 alpha and PGE2 between two groups, nor between arterial and venous blood either before or after HV. We concluded that voluntary HV stimulates the release of PGI2 and PGE2 from lung in humans and respiratory alkalosis has no significant effect on the release of PGs.


Successful use of caplacizumab in a case of refractory acquired thrombotic thrombocytopenic purpura following subacute thyroiditis.
Acquired thrombotic thrombocytopenic purpura (aTTP) is a rare condition mainly characterized by microangiopathic hemolytic anemia, thrombocytopenia, reported in approximately three cases per one million adults per year. Some reports describing co-occurrence of aTTP and other autoimmune disorders, as Graves' thyroiditis, are reported. To the best of our knowledge this is the first report describing co-occurrence of subacute thyroiditis and aTTP. The patient was refractory to conventional therapy with plasma exchange, steroids and rituximab but was successfully treated with the addition of caplacizumab, an anti-VWF bivalent variable-domain-only immunoglobulin fragment that inhibits interaction between VWF multimers and platelets.


O-glycoprotein biosynthesis: site localization by Edman degradation and site prediction based on random peptide substrates.
The characterization of mucin-type O-glycosylation is fraught with extreme difficulty at almost every level of analysis: from difficulties in obtaining glycopeptides suitable for study, their structural heterogeneity, lack of broad acting glycosidase tools capable of simplifying the glycans, and finally the vast complexity of performing analysis on multiply glycosylated glycopeptides. This, along with a lack of known peptide sequence motif(s) for the transferases that initiate mucin-type O-glycosylation, significantly hinders our understanding of mucin-type O-glycosylation at almost every level from their biosynthesis to their biological and biophysical properties. In this chapter, the use of partial chemical deglycosylation coupled with Edman amino acid sequencing is described to quantify sites of O-glycosylation. In addition, the use of oriented random peptide substrates is described for providing the specificities of the polypeptide α-N-acetylgalactosaminyltransferases, which can be used to estimate transferase-specific sites of O-glycosylation.