[Combination chemotherapy of S-1 plus biweekly docetaxel for advanced and recurrent gastric cancer].
The S-1 +biweekly docetaxel (DOC) combination therapy was evaluated for advanced or recurrent gastric cancer patients. This combination therapy was evaluated in vitro using the nude rat-gastric cancer xenograft system. S-1 alone or DOC alone showed antitumor activity, and the antitumor activity was synergistic when two drugs were combined. In clinical settings, the schedule was S-1 80 mg/m2 (day 1-14, orally) and DOC (day 1 and day 15, intravenously) followed by a 2-week rest. In phase I study, the dose of DOC was evaluated, and a recommended dose for phase II was determined as 35 mg/m2. The entry for phase II study was completed, and the preliminary results of 33 patients showed the response rate of 21.2%. The incidence of more than grade 3 adverse effects was 29%(neutropenia, leukocytopenia, anorexia and mucositis). The S-1 +biweekly DOC combination therapy can be a candidate for outpatient chemotherapy for advanced or recurrent gastric cancer.


Auto-immunity and intervertebral disc disease.
The immunological approach to intervertebral disc disease is based on a number of clinical and biological facts observed in human pathology. Even allowing for the fact that the number of cases reported in recent research is small, and that the methods of clinical and biological investigation have not been standardised, and that there are differences of opinion concerning the nature of the disc antigen, encouraging results have nonetheless been reached in support of the immunity hypothesis. The importance of the immunity phenomenon in the multifactorial pathogenesis of disc disease still remains open to discussion. In the present paper the immunological data recently acquired on disc disease is reviewed.


The Physical Environment of Nursing Homes for People with Dementia: Traditional Nursing Homes, Small-Scale Living Facilities, and Green Care Farms.
It is well recognized that the physical environment is important for the well-being of people with dementia. This influences developments within the nursing home care sector where there is an increasing interest in supporting person-centered care by using the physical environment. Innovations in nursing home design often focus on small-scale and homelike care environments. This study investigated: (1) the physical environment of different types of nursing homes, comparing traditional nursing homes with small-scale living facilities and green care farms; and (2) how the physical environment was being used in practice in terms of the location, engagement and social interaction of residents. Two observational studies were carried out. Results indicate that the physical environment of small-scale living facilities for people with dementia has the potential to be beneficial for resident's daily life. However, having a potentially beneficial physical environment did not automatically lead to an optimal use of this environment, as some areas of a nursing home (e.g., outdoor areas) were not utilized. This study emphasizes the importance of nursing staff that provides residents with meaningful activities and stimulates residents to be active and use the physical environment to its full extent.


Fine needle aspiration cytology of a case of micropapillary variant of urothelial carcinoma of bladder.
Neoplastic urothelium has the capacity to demonstrate enormous plasticity. A variety of unusual morphological variants of urothelial carcinoma have been described. Micropapillary variant of urothelial carcinoma is a rare and recently described bladder tumor, associated with poor prognosis. We present the cytological features of micropapillary urothelial carcinoma in a 65-year-old man with bladder mass. The cytological features include tightly cohesive clusters of micropapillary component admixed with urothelial carcinoma. Histopathological sections showed small nests of tumor cells residing within the lacunae. Establishing a diagnosis of micropapillary urothelial carcinoma indicates a high-grade and high-stage tumor with poor outcome, requiring an aggressive therapy. It is thus important for the cytopathologist to recognise micropapillary variant of urothelial carcinoma, for early and better management of patients with bladder tumor.


Prevalence of sexualized violence among women. A population-based study in a primary healthcare district.
In order to estimate the prevalence of sexual and physical abuse, postal questionnaires were sent to a random sample of 251 adult women in a primary care district. Three yes/no-questions were asked on these topics, and a fourth inquired into effects on health. Space was left for open-ended answers in which yes-responders were invited to write about their experiences. A total of 175 women (70%) answered, and 25 (14%) of these reported abuse. Nine (5%) had experienced women battering. Thirteen (7.5%) reported sexual abuse as an adult, and 12 (7%) as a child. Many told their stories. Methodological shortcomings in this study might explain why the rates are somewhat lower than in other investigations. However, our figures verified that abuse of women is a common social phenomenon. They also confirmed abuse as a major health problem for women. One-third of respondents explicitly reported effects on health. Others, though negating such effects, described them in written narratives. In order to study this contradiction, in-depth interviews with abused women are recommended.


The health care industry.
This series of articles is concerned with technological change in industry over the last 20 years, its effect on the health of the worker, and the measures taken by the employer to control any risk arising therefrom. Technological change cannot be viewed in isolation. Although advances in technology and the introduction of new processes are the outward and most visible sign of change in work practices, in most cases it is managerial restructuring, political pressures, and changes in legislation which bring about far greater change and which in the long term may have a greater effect on the health of the worker. No industry illustrates this better than the National Health Service and more recently the rapidly expanding private health care sector.


Membrane properties of a barnacle photoreceptor examined by the voltage clamp technique.
1. Electrical properties of the membrane of photoreceptor cells in the lateral ocelli of barnacles, Balanus amphitrite and B. eburneus were investigated by intracellular recording, polarization and voltage-clamp techniques.2. The resting potential of a dark adapted cell was 36.3 +/- 6.6 mV (S.D.) and depended mainly on the external K(+) concentration.3. Current-voltage relations obtained from voltage-clamp experiments in the absence of light were non-linear and varied with time after the onset of a step change in membrane potential; the steady state was reached after about 0.5 sec.4. Illumination resulted in a membrane potential change under current clamp and in a change of membrane current (light-initiated membrane current (L.I.C.): total membrane current with illumination minus current without illumination) under voltage-clamp conditions. Amplitudes and time course of L.I.C. depended on the light intensity as well as membrane potential.5. The L.I.C.-voltage relation was non-linear and corresponded with a slope conductance increase with increasing positive membrane potential.6. The reversal potential of L.I.C. was independent of the light intensity and the time after onset of illumination; the average value obtained in normal saline was +26.9 +/- 5.0 mV.7. The membrane conductance estimated from instantaneous L.I.C.-voltage relations agreed with the chord conductance of the non-linear L.I.C.-voltage relation.8. Decreasing external Na(+) concentration decreased the inward component of L.I.C. but not the outward component.9. Decreasing external Ca(2+) concentration increased the inward as well as the outward component of L.I.C.10. The reversal potential shifted in the negative direction with decreasing external Na(+) concentration (the rate was 10-15 mV for a tenfold change in concentration) and the rate was augmented in the absence of Ca(2+) but did not exceed 21 mV.11. The change of reversal potential with changes of external Ca(2+) concentration was negligible in normal Na(+) media but was significant in the absence of Na(+) (rate as high as 20 mV).12. Alteration of the external K(+) or Cl(-) concentrations did not affect the amplitude or reversal potential of L.I.C.13. The results indicate that illumination increases the membrane permeability mainly to Na(+) ions and that the primary effect of Ca(2+) ions is suppression of the permeability increase; Ca(2+) permeability may increase slightly during illumination.


Investigating the breast cancer screening-treatment-mortality pathway of women diagnosed with invasive breast cancer: Results from linked health data.
To examine the screening-treatment-mortality pathway among women with invasive breast cancer in 2006-2014 using linked data. BreastScreen histories of South Australian women diagnosed with breast cancer (n = 8453) were investigated. Treatments recorded within 12 months from diagnosis were obtained from linked registry and administrative data. Associations of screening history with treatment were investigated using logistic regression and with cancer mortality outcomes using competing risk analyses, adjusting for socio-demographic, cancer and comorbidity characteristics. For screening ages of 50-69 years, 70% had participated in BreastScreen SA ≤ 5 years and 53% ≤ 2 years of diagnosis. Five-year disease-specific survival post-diagnosis was 90%. Compared with those not screened ≤5 years, women screened ≤2 years had higher odds, adjusted for socio-demographic, cancer and comorbidity characteristics, and diagnostic period, of breast-conserving surgery (aOR 2.5, 95% CI 1.9-3.2) and radiotherapy (aOR 1.2, 95% CI 1.1-1.3). These women had a lower unadjusted risk of post-diagnostic cancer mortality (SHR 0.33, 95% CI 0.27-0.41), partly mediated by stage (aSHR 0.65, 95% CI 0.51-0.81), and less breast surgery (aSHR 0.78, 95% CI 0.62-0.99). Screening ≤2 years and conserving surgery appeared to have a greater than additive association with lower post-diagnostic mortality (interaction term SHR 0.42, 95% CI 0.23-0.78). The screening-treatment-mortality pathway was investigated using linked data.


Lack of left ventricular dysfunction associated with sustained exposure to hyperlipidemia following lung transplantation.
Hyperlipidemia due to standard immunosuppressive agents occurs commonly following solid organ transplantation. A decision to treat hyperlipidemias would be based on the assumption that such disorders lead to accelerated atherogenesis and ultimately to cardiac dysfunction. We therefore sought to examine whether hyperlipidemias following lung transplantation were associated with a decline in left ventricular (LV) function. We retrospectively reviewed serial echocardiograms, radionucleotide angiograms (RNAs), and serum lipid levels following lung transplantation. Results of cardiac studies were defined as abnormal if a decline in LV grade occurred from the best result at any time postoperatively to the most recent study. A total of 184 patients with transplants between November 1983 and June 1995 were reviewed. Eighty patients were excluded owing to incomplete data. One patient was excluded because of severe perioperative myocardial dysfunction. Approximately 80% of patients had elevated cholesterol levels and 60% had elevated low-density lipoprotein levels. Triglyceride levels were raised in 34% of patients while only 4% had an abnormal serum high-density lipoprotein level. More than 80% of patients had no evidence of LV abnormalities in either RNA or echocardiographic studies (group 1). One patient had a change in echocardiographic LV function but no change in grade of RNA (group 2). Twenty patients had a decline in grade based on RNA but no change in the echocardiogram (group 3). There were no patients with changes in both RNA and echocardiogram (group 4). All changes in LV function were from grade I to II. The mean period of follow-up exceeded 30 months for patients in groups 1 to 3. Follow-up data at 3, 4, and 5 years were available on 47, 23, and 12 patients, respectively. There were no differences between the proportions of subjects with normal and abnormal serum lipid levels in each group. In the initial 5 years after lung transplantation, dyslipidemias affect the majority of patients but are not associated with evidence of deteriorating LV function.


Stable assembly of PsaE into cyanobacterial photosynthetic membranes is dependent on the presence of other accessory subunits of photosystem I.
We studied assembly of the PsaE subunit of photosystem I into photosynthetic membranes of cyanobacterial mutant strains that lack specific photosystem I subunits. Radiolabeled PsaE was incubated with photosynthetic membranes, and their binding and assembly were assayed by resistance to removal by chaotropic agents and proteolytic digestion. PsaE incorporated into the wild-type membranes was resistant to these treatments. In the absence of PsaD, it was resistant to proteolytic digestion, but was removed by NaBr. When the membranes were isolated from a mutant strain in which the psaF and psaJ genes have been inactivated, PsaE assembled in vitro could not be removed. PsaE could associate with the membranes of the strain DF in which the psaD, psaJ and psaF genes have been mutated. However, the radiolabeled PsaE associated with these membranes was removed both by the proteolytic as well as by the chaotropic agents. Characterization of PsaE present in vivo revealed similar results. These observations suggest that PsaD and PsaF/J may interact with PsaE and stabilize it in the photosystem I complex.


Lixivaptan: a novel vasopressin receptor antagonist.
Arginine vasopressin, also known as antidiuretic hormone, is a neuropeptide that functions in the maintenance of body water homeostasis. Inappropriate secretion of vasopressin has been implicated in the pathophysiology of multiple diseases, including polycystic kidney disease, syndrome of inappropriate antidiuretic hormone (SIADH) secretion, and the hyponatremia commonly associated with cirrhosis and congestive heart failure. Vasopressin receptor antagonists are novel agents that block the physiologic actions of vasopressin. Lixivaptan is a vasopressin receptor antagonist with high V2 receptor affinity and is now undergoing Phase III clinical trials. Studies so far have demonstrated that lixivaptan is efficacious in the correction of hyponatremia in SIADH, heart failure and liver cirrhosis with ascites, and few adverse effects have been noted. Thus, lixivaptan remains a promising therapeutic modality for the treatment of multiple diseases and prevention of the associated morbidity and mortality associated with hyponatremia.


Seasonal variations in plant species effects on soil N and P dynamics.
It is well established that plant species influence ecosystem processes, but we have little ability to predict which vegetation changes will alter ecosystems, or how the effects of a given species might vary seasonally. We established monocultures of eight plant species in a California grassland in order to determine the plant traits that account for species impacts on nitrogen and phosphorus cycling. Plant species differed in their effects on net N mineralization and nitrification rates, and the patterns of species differences varied seasonally. Soil PO4- and microbial P were more strongly affected by slope position than by species. Although most studies focus on litter chemistry as the main determinant of plant species effects on nutrient cycling, this study showed that plant species affected biogeochemical cycling through many traits, including direct traits (litter chemistry and biomass, live-tissue chemistry and biomass) and indirect traits (plant modification of soil bioavailable C and soil microclimate). In fact, species significantly altered N and P cycling even without litter inputs. It became particularly critical to consider the effects of these multiple traits in order to account for seasonal changes in plant species effects on ecosystems. For example, species effects on potential rates of net N mineralization were most strongly influenced by soil bioavailable C in the fall and by litter chemistry in the winter and spring. Under field conditions, species effects on soil microclimate influenced rates of mineralization and nitrification, with species effects on soil temperature being critical in the fall and species effects on soil moisture being important in the dry spring. Overall, this study clearly demonstrated that in order to gain a mechanistic, predictive understanding of plant species effects on ecosystems, it is critical to look beyond plant litter chemistry and to incorporate the effects of multiple plant traits on ecosystems.


Heterogeneous graph embedding model for predicting interactions between TF and target gene.
Identifying the target genes of transcription factors (TFs) is of great significance for biomedical researches. However, using biological experiments to identify TF-target gene interactions is still time consuming, expensive and limited to small scale. Existing computational methods for predicting underlying genes for TF to target is mainly proposed for their binding sites rather than the direct interaction. To bridge this gap, we in this work proposed a deep learning prediction model, named HGETGI, to identify the new TF-target gene interaction. Specifically, the proposed HGETGI model learns the patterns of the known interaction between TF and target gene complemented with their involvement in different human disease mechanisms. It performs prediction based on random walk for meta-path sampling and node embedding in a skip-gram manner. We evaluated the prediction performance of the proposed method on a real dataset and the experimental results show that it can achieve the average area under the curve of 0.8519 ± 0.0731 in fivefold cross validation. Besides, we conducted case studies on the prediction of two important kinds of TF, NFKB1 and TP53. As a result, 33 and 32 in the top-40 ranking lists of NFKB1 and TP53 were successfully confirmed by looking up another public database (hTftarget). It is envisioned that the proposed HGETGI method is feasible and effective for predicting TF-target gene interactions on a large scale. The source code and dataset are available at https://github.com/PGTSING/HGETGI. Supplementary data are available at Bioinformatics online.


Development of the gonadotropin-releasing hormone system.
This review summarizes the current understanding of the development of the neuroendocrine gonadotropin-releasing hormone (GnRH) system, including discussion on open questions regarding (1) transcriptional regulation of the Gnrh1 gene; (2) prenatal development of the GnRH1 system in rodents and humans; and (3) paracrine and synaptic communication during migration of the GnRH cells.


Acute renal failure after high-dose methotrexate therapy in a patient with ileostomy.
High-dose methotrexate (HD-MTX) is an important treatment for Burkitt lymphoma, but can cause hepatic and renal toxicity when its clearance is delayed. We report a case of acute renal failure after HD-MTX therapy in a patient with ileostomy, The patient was a 3-year-old boy who had received a living-related liver transplantation for congenital biliary atresia. At day 833 after the transplantation, he was diagnosed with PTLD (post-transplantation lymphoproliferative disorder, Burkitt-type malignant lymphoma). During induction therapy, he suffered ileal perforation and ileostomy was performed. Subsequent HD-MTX therapy caused acute renal failure that required continuous hemodialysis. We supposed that intravascular hypovolemia due to substantial drainage from the ileostoma caused acute prerenal failure. After recovery of his renal function, we could safely treat the patient with HD-MTX therapy by controlling drainage from ileostoma with total parenteral nutrition.


[The determination of amylo-1,6-glucosidase in biopsy specimens from human chorion].
This method has been developed for the prenatal diagnosis of a grave hereditary disease, a deficiency of amylo-1,6-glucosidase (A-1,6-G) activity. The methods suggested earlier did not rule out the effects of other glucosidases, that could result in false-positive data if the fetus was involved. The new method for measuring A-1,6-G activity includes sedimentation of acid alpha-glucosidase with rabbit blood antiserum to human placental acid alpha-glucosidase. A-1,6-G activity is estimated from the difference in glucose accrement with limit dextrin and glycogen used as substrates. A-1,6-G activities were measured in 15 chorion samples obtained in the first trimester of pregnancy by the developed method, and normal values of this parameter established, making up 39.77 +/- 8.1 nmol/h per g of protein. The method may be useful in the prenatal diagnosis of type III glycogenosis.


Germination of Echinochloa crus-galli (Barnyard Grass) Seeds under Anaerobic Conditions : Respiration and Response to Metabolic Inhibitors.
Echinochloa crus-galli L. Beauv., a rice-field weed, can germinate and grow for extended periods of time in an anaerobic environment. Compared to pea, which does not germinate under anaerobiosis, the evolution of CO(2) in Echinochloa and rice is lower and the peak rate of CO(2) evolution is delayed when germinated without oxygen. The plants studied also differ with respect to their respiration ratio ([CO(2)] N(2)/[CO(2)] air) and metabolism used during the early stages of germination. Echinochloa does not increase its glycolytic rate under anaerobiosis, whereas pentose phosphate pathway activity appears to increase during the first 40 to 50 hours of germination.Based on its response to metabolic inhibitors (NaF, dinitrophenol, and malonate), anaerobic metabolism in Echinochloa proceeds primarily through glycolysis, with partial operation of the tricarboxylic acid cycle and little or no oxidative phosphorylation. Also, Echinochloa is sensitive to CN during aerobic germination, whereas rice appears to be able to shift to CN-insensitive electron transport. Finally, the effectiveness of cyanide and azide on inhibiting germination of Echinochloa in N(2), but not CO, suggests that cytochrome oxidase is not used to reoxidize pyridine nucleotides in the absence of oxygen. The possible existence of an alternate electron acceptor is discussed.


Interleukin I and the glomerular mesangium. II. Monokine stimulation of mesangial cell prostanoid secretion.
Monocytic (MC) infiltration is a prominent feature of many forms of immune-mediated glomerulonephritis. Through the release of interleukin-1, (IL-1), monocyte/macrophages have been shown to induce the proliferation of mesangial cells and to stimulate the secretion of a glomerular basement membrane-degrading neutral proteinase. In addition, mesangial cells release a cytokine that expresses many of the biologic properties of monocyte IL-1, including stimulation of mesangial cell proliferation. Because many of the actions of IL-1 are mediated by the induction of prostanoid prostaglandin (PG) synthesis, the authors determined the effects of purified macrophage and mesangial IL-1 on the secretion of prostaglandin E (PGE), prostacyclin, and thromboxane. The results indicated that cycling MCs release primarily PGE in response to purified IL-1. The local release by either monocytes or mesangial cells of IL-1 during glomerular inflammation, with subsequent mesangial cell generation of vasodilatory PGE, may be responsible in part for the alterations in the glomerular microcirculation observed in these disorders.


S-nitrosylation of cytoskeletal proteins.
Nitric oxide has pronounced effects on cellular functions normally associated with the cytoskeleton, including cell motility, shape, contraction, and mitosis. Protein S-nitrosylation, the covalent addition of a NO group to a cysteine sulfur, is a signaling pathway for nitric oxide that acts in parallel to cyclic guanosine monophosphate (cGMP), but is poorly studied compared to the latter. There is growing evidence that S-nitrosylation of cytoskeletal proteins selectively alters their function. We review that evidence, and find that S-nitrosylation of cytoskeletal targets has complementary but distinct effects to cyclic-GMP in motile and contractile cells-promoting cell migration, and biasing muscle contraction toward relaxation. However, the effects of S-nitrosylation on a host of cytoskeletal proteins and functions remains to be explored.


Fine needle aspiration cytology of primary thyroid lymphoma: a report of ten cases.
Primary lymphoma is an uncommon malignancy of the thyroid, comprising of 0.6 to 5 per cent of thyroid cancers in most series. Primary thyroid lymphomas (PTL) occur most commonly in elderly women and are commonly of B- cell origin. These frequently present in clinical stage IE and IIE. We report here ten cases of PTL diagnosed over a period of about 7 years in our institute. Out of these ten cases, nine were diagnosed on fine needle aspiration cytology (FNAC) and one case was misdiagnosed as lymphocytic thyroiditis. This case was diagnosed as Non- Hodgkin's lymphoma on surgical specimen. Five patients are disease free and doing well, while two died of disease and the other two were lost to follow-up. One patient is currently on chemotherapy. The salient clinical, biochemical, radiological features, FNA findings along with diagnostic difficulties are discussed.


Late failure of autologous marrow grafts in lethally irradiated dogs given anti-class II monoclonal antibody.
We established a model of canine marrow autografts after 9.2 Gy total body irradiation (TBI) to study the role of class II antigens in hematopoietic stem cell growth and differentiation. Twenty dogs were given 9.2 Gy TBI, marrow, and intravenous (IV) murine anti-class II monoclonal antibody (MoAb). Infusion of 0.6 mg/kg/d of MoAb H81.98.21, an IgG2a reactive with HLA-DR, on days 0 to 4 after TBI did not prevent initial engraftment, but dogs died with late graft failure. MoAb B1F6, an IgG2a reactive with HLA-DR + DP, had no adverse effect on engraftment, although both MoAbs detect antigens on stem cells. The critical time for the effect of MoAbs is the first 4 days after transplantation. Our findings argue against several pathogenetic mechanisms, including removal of MoAb-coated stem cells by the reticuloendothelial system (RES), canine complement-mediated cytotoxic effects on stem cells, antibody-dependent cellular cytotoxicity, and inactivation of MoAb-coated cells by dog anti-mouse antibody. To distinguish between MoAb-induced damage to microenvironment (ME)/accessory cells (AC) and late graft failure from a lack of pluripotent stem cells, three dogs were given TBI, a marrow autograft, and MoAb H81.98.21 on days 0 to 4; one, given thoracic duct cells on day 6, developed graft failure; the other two, given marrow depleted of AC by L-leucyl L-leucine o-methyl ester (Leu-Leu-OMe), had sustained grafts. Findings support the notion that originally transplanted pluripotent stem cells are no longer present on day 6 and that the ME is functional and able to support newly injected stem cells.


Qualitative analysis of the care of children in hospital in four countries-Part 2.
As part of a large study of the care of children in Australian, British, Indonesian, and Thai hospitals, qualitative methods were used to examine differences influenced by culture. Two groups were surveyed: parents of hospitalized children, and staff caring for them. Vignettes were used to invoke discussion, and content analysis was used to examine the data. Subjects were interviewed singly, or in focus groups. These interviews were audiotaped and transcribed for analysis. This article is the second of a two-part series, and includes results of the staff's interviews and discussion. The parents' results and discussion were published in Part 1 (Shields & King, 2001). Staff in all the countries considered communication with parents to be an important part of care of the hospitalized child, and this was consistent with the parents' responses. Staff were mindful of safe practices, though more so in Australia and Britain than Indonesia and Thailand. Cost of treatment for the parents was an important consideration for staff in Indonesia and Thailand when they were planning care for the child. Cultural constructions were more likely to be considered by the Australian and British staff than the Indonesian and Thai staff, and this may have been influenced by the prevailing culture of medical dominance in those countries.


[Management of anesthesia for surgery of the abdominal aorta].
Anesthesia and post operative care of patients requiring abdominal aorta surgery are frequently complicated because of associated ischemic cardiopathy or respiratory insufficiency. Pre operative evaluation indicates the optimal peri-operative strategy and the need to appropriate peri-operative monitoring. This applies to patients with a previous history of myocardial infarction or with a poorly or not controlled cardiac insufficiency. The use of Swan-Ganz catheters allows monitoring of the hemo-dynamic parameters during operation, especially at the moment of clamping or unclamping of the aorta. Vasodilators and optimal volume loading allow myocardial adaptation and reduce the incidence of myocardial infarction, the main cause of peri-operative death. To perform these operations in the best conditions requires a close medicosurgical cooperation in specialized teams.


Canadian Dairy Network for Antimicrobial Stewardship and Resistance (CaDNetASR): An On-Farm Surveillance System.
Canada has implemented on-farm antimicrobial resistance (AMR) surveillance systems for food-producing animals under the Canadian Integrated Program for Antimicrobial Resistance (CIPARS); however, dairy cattle have not been included in that program yet. The objective of this manuscript was to describe the development and implementation of the Canadian Dairy Network for Antimicrobial Stewardship and Resistance (CaDNetASR). An Expert Panel (EP) of researchers was created to lead the development of the dairy surveillance system. The EP initiated a draft document outlining the essential elements of the surveillance framework. This document was then circulated to a Steering Committee (SC), which provided recommendations used by the EP to finalize the framework. CaDNetASR has the following components: (1) a herd-level antimicrobial use quantification system; (2) annually administered risk factor questionnaires; and (3) methods for herd-level detection of AMR in three sentinel enteric pathogens (generic Escherichia coli, Campylobacter spp., and Salmonella spp.) recovered from pooled fecal samples collected from calves, heifers, cows, and the manure pit. A total of 144 dairy farms were recruited in five Canadian provinces (British-Columbia, Alberta, Ontario, Québec, and Nova-Scotia), with the help of local herd veterinarians and regional field workers, and in September 2019, the surveillance system was launched. 97.1 and 94.4% of samples were positive for E. coli, 63.8, and 49.1% of samples were positive for Campylobacter spp., and 5.0 and 7.7% of samples were positive for Salmonella spp., in 2019 and 2020, respectively. E. coli was equally distributed among all sample types. However, it was more likely that Campylobacter spp. were recovered from heifer and cow samples. On the other hand, it was more common to isolate Salmonella spp. from the manure pit compared to samples from calves, heifers, or cows. CaDNetASR will continue sampling until 2022 after which time this system will be integrated into CIPARS. CaDNetASR will provide online access to farmers and veterinarians interested in visualizing benchmarking metrics regarding AMU practices and their relationship to AMR and animal health in dairy herds. This will provide an opportunity to enhance antimicrobial stewardship practices on dairy farms in Canada.


The lateral intraparietal sulcus takes viewpoint changes into account during memory-guided attention in natural scenes.
Previous studies demonstrated that long-term memory related to object-position in natural scenes guides visuo-spatial attention during subsequent search. Memory-guided attention has been associated with the activation of memory regions (the medial-temporal cortex) and with the fronto-parietal attention network. Notably, these circuits represent external locations with different frames of reference: egocentric (i.e., eyes/head-centered) in the dorsal attention network vs. allocentric (i.e., world/scene-centered) in the medial temporal cortex. Here we used behavioral measures and fMRI to assess the contribution of egocentric and allocentric spatial information during memory-guided attention. At encoding, participants were presented with real-world scenes and asked to search for and memorize the location of a high-contrast target superimposed in half of the scenes. At retrieval, participants viewed again the same scenes, now all including a low-contrast target. In scenes that included the target at encoding, the target was presented at the same scene-location. Critically, scenes were now shown either from the same or different viewpoint compared with encoding. This resulted in a memory-by-view design (target seen/unseen x same/different view), which allowed us teasing apart the role of allocentric vs. egocentric signals during memory-guided attention. Retrieval-related results showed greater search-accuracy for seen than unseen targets, both in the same and different views, indicating that memory contributes to visual search notwithstanding perspective changes. This view-change independent effect was associated with the activation of the left lateral intra-parietal sulcus. Our results demonstrate that this parietal region mediates memory-guided attention by taking into account allocentric/scene-centered information about the objects' position in the external world.


HIV seroprevalence and risk factors among clients of female and male prostitutes.
To document the HIV and STD infection rates among clients of female (CFP) and clients of male prostitutes (CMP) and to identify the risk factors for HIV among CFP and CMP. Structured interviews were conducted with 82 CMP and 69 CFP in 1990 and 1991 in Atlanta, Georgia, U.S.A. Blood samples were tested for HIV, syphilis, and hepatitis B. The HIV-positive rate was 36.6% among CMP and 2.9% among CFP. Syphilis seromarkers were found in 15.9% of CMP and 10.1% of CFP; hepatitis B seromarkers were identified in 58.0% of CMP and 24.6% of CFP. Key risk factors for HIV among CMP included serologic history of syphilis, serologic history of hepatitis B, receptive anal sex with a male prostitute, ever injecting drugs, ever using crack cocaine, and little education. CFP had no significant risk factors for HIV in the logistic analysis. Several studies have focused on risk factors for HIV among female and male prostitutes; however, research on their clients has been limited. Although HIV infection rates among CFP are relatively low, their infection rate for syphilis and hepatitis warrants serious health education efforts. Even more critical are harm-reduction programs targeting CMP. Generic health and HIV risk reduction messages on heterosexual transmission might be insufficient.


Pseudoheptacoordination and pseudohexacoordination in tris(2-N,N-dimethylbenzylamino)phosphane.
The phosphane (C(6)H(4)-2-CH(2)NMe(2))(3)P (1) upon recrystallization from various solvents yielded the structurally different forms 1A, 1C, 1B(1), and 1B(2). Phosphane oxide (C(6)H(4)-2-CH(2)NOMe(2))(3)PO (2) was obtained from 1 by oxidation with hydrogen peroxide. X-ray analysis provided molecular structures for 1A, 1B(1), 1B(2), and 2. Phosphanes 1A and 1B(1) have pseudohexacoordinate frameworks as a result of the formation of two P-N donor interactions, 1B(2) has a pseudoheptacoordinate geometry due to the presence of three P-N interactions, and 2 resides in a tetrahedral geometry. The presence of the flexible dimethylaminobenzyl group in 1A, 1C, 1B(1), and 1B(2) is reasoned to be responsible for this variation in coordination geometry. Phosphane oxide 2 has very strong donor oxygen atoms from N-oxide groups but they are involved in competition with the presence of hydrogen bonding, which results in the lack of donor coordination. High-resolution (1)H, (13)C, and (31)P NMR measurements are also reported. The results provide evidence for the low-energy threshold required to allow hypercoordinated phosphorus to alter coordination geometry.


Treatment of colored and real industrial effluents through electrocoagulation using solar energy.
This study was undertaken to investigate the removal of Acid Orange 2 (sodium 4-[(2E)-2-(2-oxonaphthalen-1-ylidene) hydrazinyl] benzenesulfonate) and Reactive Blue 19 (2-Anthracenesulfonicacid,1-amino-9,10-dihydro-9,10-dioxo-4-[[3-[[2-(sulfooxy) ethyl] sulfonyl] phenyl] amino]-,sodium salt (1:2)) from synthesized and real effluents through electrocoagulation using solar cells for the purpose of improving economic efficiency of the process. The impact of a number of key operating parameters was explored including current density, anode type, temperature, pH, and electrolyte concentration. The current density of 45 Am(-2) proved to be the optimum level for both dyes. The same optimum alternatives were found for the other parameters in both cases: iron anode, a temperature level of 25°C, a pH of 7, and an electrolyte concentration of 15 mg L(-1). Both effluent samples were subjected to COD (chemical oxygen demand) and TOC (total organic carbon) tests. Cost analysis was performed for the treatment process.


Formation and function of dauer ascarosides in the nematodes Caenorhabditis briggsae and Caenorhabditis elegans.
The biosynthetic pathways and functions of ascaroside signaling molecules in the nematode Caenorhabditis elegans have been studied to better understand complex, integrative developmental decision-making. Although it is known that ascarosides play multiple roles in the development and behavior of nematode species other than C. elegans, these parallel pheromone systems have not been well-studied. Here, we show that ascarosides in the nematode Caenorhabditis briggsae are biosynthesized in the same manner as C. elegans and act to induce the alternative developmental pathway that generates the stress-resistant dauer lifestage. We show that ascr#2 is the primary component of crude dauer pheromone in C. briggsae; in contrast, C. elegans dauer pheromone relies on a combination of ascr#2, ascr#3, and several other components. We further demonstrate that Cbr-daf-22, like its C. elegans ortholog Cel-daf-22, is necessary to produce short-chain ascarosides. Moreover, Cbr-daf-22 and Cel-daf-22 mutants produce an ascaroside-independent metabolite that acts antagonistically to crude dauer pheromone and inhibits dauer formation.


Flow-controlled ventilation - a new and promising method of ventilation presented with a review of the literature.
Substantial efforts have been undertaken to identify and minimise factors responsible for the development of ventilator-induced lung injury. A novel approach to this problem addresses energy dissipated in lung tissue during the breathing cycle as one of the key problems. Flow-controlled ventilation is a new modality of mechanical ventilation based on a constant flow during both inspiration and expiration. This review aims to evaluate the current evidence available regarding flow-controlled ventilation. Lastly, three cases of flow-controlled ventilation application are presented: ventilation with a small lumen tube during tracheal resection, one-lung ventilation during thoracoscopic lobectomy, and ventilation of a critically ill patient with acute respiratory distress syndrome in an intensive care unit setting.


Prostate lesions with cribriform / pseudocribriform pattern.
Prostate lesions with cribriform / pseudocribriform architecture range from normal histological structures to infiltrative carcinoma. In each group of lesions with cribriform architecture (benign, premalignant and malignant intraductal or infiltrating), there are situations in which histological classification of the lesion is difficult or impossible on routine stains. A more wide-scale application of the immunohistochemical investigation for clearing up the problematic prostate lesions led to the definition and reclassification of cribriform lesions in distinct categories and sometimes very different in terms of progression, prognosis and treatment. This paper proposes an overview of the prostate lesions with cribriform / pseudocribriform architecture, emphasizing the morpho-immunohistochemical criteria for positive and differential diagnosis.


A great improvement of fusion efficiency in mouse B cell hybridoma production by use of the new culture medium, GIT.
The recently established culture medium, GIT, is applicable to many kinds of cells including mouse and human myeloma cells, and most adhesive cell lines. We applied this GIT medium to mouse B cell hybridoma production. When the medium was used to propagate myeloma cells before cell fusion and also for HAT selective medium, the fusion efficiency was more than twice as high as when the regular medium (RPMI-1640 supplemented with FBS) was used. Constantly more than 80% wells were hybridoma positive irrespective of the antigens used. To determine the optimal cell concentration at the hybridoma selection, a graded number of myeloma and spleen cells was distributed to each well; the best result was obtained when 3 X 10(4) myeloma and 3 X 10(5) spleen cells were distributed to each well. In addition, the GIT medium shows very little lot-to-lot variation. These results indicate that fusion efficiency in mouse B cell hybridoma production was greatly improved by using GIT medium.


Guidelines for referral of the patient with an adnexal mass.
Gynecologists have to differentiate between benign and malignant adnexal masses. We review the evidence supporting to the specialty care of a gynecologic oncologist on the basis of the physical examination, imaging studies, family history, and CA 125 determination. We recommend adherence to the ACOG/SGO Joint Opinion guidelines. Specifically, referral to a gynecologic oncologist seems warranted for postmenopausal women with elevated CA 125, nodular or fixed pelvic mass, metastatic disease, ascites, or family history of breast or ovarian cancer. Premenopausal women should be referred if the CA 125 is elevated above 200 U/mL, there is an evidence of metastatic disease or ascites, or strong family history of breast or ovarian cancer.


Quantum coherence enabled determination of the energy landscape in light-harvesting complex II.
The near-unity efficiency of energy transfer in photosynthesis makes photosynthetic light-harvesting complexes a promising avenue for developing new renewable energy technologies. Knowledge of the energy landscape of these complexes is essential in understanding their function, but its experimental determination has proven elusive. Here, the observation of quantum coherence using two-dimensional electronic spectroscopy is employed to directly measure the 14 lowest electronic energy levels in light-harvesting complex II (LHCII), the most abundant antenna complex in plants containing approximately 50% of the world's chlorophyll. We observe that the electronically excited states are relatively evenly distributed, highlighting an important design principle of photosynthetic complexes that explains the observed ultrafast intracomplex energy transfer in LHCII.


In vitro skin permeation and anti-atopic efficacy of lipid nanocarriers containing water soluble extracts of Houttuynia cordata.
The aims of this work are to enhance the in vitro skin permeation of Houttuynia cordata (water-soluble extract of H. cordata; HCWSE) and to boost the efficacy of HCWSE against atopic dermatitis (AD) - like skin lesion in hairless mice using lipid nano-carriers (liposome and cubosome). HCWSE was obtained by a hot water extraction. Monoolein cubosomal suspension containing HCWSE and egg phosphatidylcholine liposomal suspension containing the same was prepared by a sonication and a film hydration method, respectively. The lipid nano-carriers, especially cubosome, enhanced the in vitro skin permeation of HCWSE. The inhibitory effects of HCWSE-containing lipid carrier suspensions on the development of 1-chloro-2,4-dinitrobenzene (DNCB)-induced AD-like skin lesion in hairless mice were investigated by observing appearance of skin surface, serum immunoglobulin E (IgE) level and cytokine expression. HCWSE-containing preparations suppressed IgE production and interleukin 4 expression, whereas they promoted interferon gamma expression. The order of lymphocyte (B-cell, Th1 cell and Th2 cell) modulating effect was HCWSE-containing cubosomal suspension > HCWSE-containing liposomal suspension > HCWSE solution in phosphate buffered saline, indicating that the cubosomal suspension, among the preparations, was the most efficacious in inhibiting the development of DNCB-induced AD-like skin lesion. It is believed that the cubosomal suspension containing HCWSE would be an efficacious preparation for the treatment of AD.


Influence of mouse placental factors on in vitro antibody synthesis.
Placental culture supernatants (PS) obtained from various mouse crossbreedings were added to mouse IgG1 hybridoma cultures producing anti-DNP antibodies. The quantity of monoclonal antibody (mAb) produced, the nature of these antibodies and the proliferation of the hybridoma cells were studied. It was observed that the supernatants increased or diminished the production of mAb, depending on the genetic origin of the placentae. This effect was the same using placentae from primiparous or multiparous females and it was not due to modifications of the cellular proliferation of the hybridoma, as shown by 3H-thymidine uptake. It was also found that placental supernatants induced an increase in the proportion of asymmetric, blocking antibodies synthesized by the hybridoma. This effect was detected with supernatants from both allogeneic or syngeneic crossbreedings, but only when placentae were obtained from multiparous females. These observations indicate that placentae produce at least two soluble factors that participate in the regulation of antibody synthesis and suggest that these factors play an important role in the immune equilibrium between mother and fetus.


[The aldehyde dehydrogenase activity in the erythrocytes of alcoholic patients].
Red cell aldehyde dehydrogenase (ALDH, EC 22.214.171.124) activity was measured by spectrophotometry in normal subjects and alcoholics after various periods of alcohol abstinence. ALDH was measured in all red cell hemolysate fractions; red cells were purified from hemoglobin by Sephadex CM-50 chromatography. The enzyme activity was found reduced in alcoholics' red cells as against that in controls. ALDH activities were somewhat increasing and approaching the normal values in the patients not using ethanol for 4 weeks or longer. These results recommend ALDH measurements in human red cells as a test for the detection of subjects abusing alcohol.


Gemfibrozil-induced myopathy.
Drug-induced myopathy has been reported with use of lovastatin, nicotinic acid, and clofibrate. A particularly severe form, often accompanied by rhabdomyolysis, has been reported with the use of lovastatin and gemfibrozil; however, as far as we know, no case has been documented with use of gemfibrozil alone. Herein, we report the first case (to our knowledge of gemfibrozil-induced myopathy, confirmed by drug rechallenge.


On the Relationship Between fMRI and Theories of Cognition: The Arrow Points in Both Directions.
In this article, we ask about the contribution of fMRI data to our understanding of theories of cognition and about the contribution of theories of cognition to our understanding of fMRI data. Experiments using fMRI can contribute to our understanding of cognition when they are designed to test the predictions of a particular cognitive theory. Although not all cognitive theories make clear predictions about patterns of activity in the brain fMRI experiments are often well suited to testing the predictions of those that do. However, many fMRI studies that are concerned with cognitive functional neuroanatomy are not designed to test predictions of cognitive theories but are instead designed to investigate the role played by different regions of the brain in cognitive activity. These fMRI studies do not shed light on cognitive theories but instead depend on cognitive theories to interpret the data-an interpretation that is only as valid as the cognitive theory on which it is based. These considerations suggest that the relationship between fMRI and theories of cognition is a two-way street.


Quantum Hall Effect Measurement of Spin-Orbit Coupling Strengths in Ultraclean Bilayer Graphene/WSe2 Heterostructures.
We study proximity-induced spin-orbit coupling (SOC) in bilayer graphene/few-layer WSe2 heterostructure devices. Contact mode atomic force microscopy (AFM) cleaning yields ultraclean interfaces and high-mobility devices. In a perpendicular magnetic field, we measure the quantum Hall effect to determine the Landau level structure in the presence of out-of-plane Ising and in-plane Rashba SOC. A distinct Landau level crossing pattern emerges when tuning the charge density and displacement field independently with dual gates, originating from a layer-selective SOC proximity effect. Analyzing the Landau level crossings and measured inter-Landau level energy gaps yields the proximity-induced SOC energy scale. The Ising SOC is ∼2.2 meV, 100 times higher than the intrinsic SOC in graphene, whereas its sign is consistent with theories predicting a dependence of SOC on interlayer twist angle. The Rashba SOC is ∼15 meV. Finally, we infer the magnetic field dependence of the inter-Landau level Coulomb interactions. These ultraclean bilayer graphene/WSe2 heterostructures provide a high mobility system with the potential to realize novel topological electronic states and manipulate spins in nanostructures.


Xylary pH and Reduction Potential Levels of Iron-stressed Silver Maple (Acer saccharinum L.).
Xylary fluid pH and reduction potentials were measured on silver maple (Acer saccharinum L.) grown under Fe and pH stress. Although pH and reduction potential (millivolt/59.2) varied significantly in the nutrient solution, xylary pH and reduction potential remained constant. It was concluded that changes in the pH and reduction potential in the xylary fluid of silver maple are not responsible for iron chlorosis.


Synergism between a half-site and an imperfect estrogen-responsive element, and cooperation with COUP-TFI are required for estrogen receptor (ER) to achieve a maximal estrogen-stimulation of rainbow trout ER gene.
In all oviparous, liver represents one of the main E2-target tissues where estrogen receptor (ER) constitutes the key mediator of estrogen action. The rainbow trout estrogen receptor (rtER) gene expression is markedly up-regulated by estrogens and the sequences responsible for this autoregulation have been located in a 0.2 kb upstream transcription start site within - 40/- 248 enhancer region. Absence of interference with steroid hormone receptors and tissue-specific factors and a conserved basal transcriptional machinery between yeast and higher eukaryotes, make yeast a simple assay system that will enable determination of important cis-acting regulatory sequences within rtER gene promoter and identification of transcription factors implicated in the regulation of this gene. Deletion analysis allowed to show a synergistic effect between an imperfect estrogen-responsive element (ERE) and a consensus half-ERE to achieve a high hormone-dependent transcriptional activation of the rtER gene promoter in the presence of stably expressed rtER. As in mammalian cells, here we observed a positive regulation of the rtER gene promoter by the chicken ovalbumin upstream promoter-transcription factor I (COUP-TFI) through enhancing autoregulation. Using a point mutation COUP-TFI mutant unable to bind DNA demonstrates that enhancement of rtER gene autoregulation requires the interaction of COUP-TFI to the DNA. Moreover, this enhancement of transcriptional activation by COUP-TFI requires specifically the AF-1 transactivation function of ER and can be observed in the presence of E2 or 4-hydroxytamoxifen but not ICI 164384. Thus, this paper describes the reconstitution of a hormone-responsive transcription unit in yeast in which the regulation of rtER gene promoter could be enhanced by the participation of cis-elements and/or trans-acting factors, such as ER itself or COUP-TF.


Tunable Heck-Mizoroki Reaction of Dibromonaphthalene Diimide with Aryl Ethylenes: Design, Synthesis, and Characterization of Coplanar NDI-Based Conjugated Molecules.
Rational design of coplanar NDI-based conjugated molecules was achieved by covalently connecting naphthalene diimide (NDI) units with aryl (Ar) groups through vinylene (V) linkers via Heck-Mizoroki reaction. Two series of products, diolefination products (ArVNDIVAr) and hydroxylated and mono-olefination products (HONDIVAr), can be obtained, respectively, in moderate to excellent yields (45-90%) under controlled conditions, in which catalyst and base play the key roles. Density functional theory calculation discloses the outstanding planarity of the two types of products. Large bathochromic shifts are observed in both the absorbance and photoluminescence spectra of the HONDIVAr (144 and 229 nm) and ArVNDIVAr (180 and 242 nm) π-systems. Bathochromic shifts can be adjusted within the broad wavelength range by introducing 4'-substituents, either electron-withdrawing group (NO2) or electron-donating group (NMe2), in the phenyl group of aryl ethylenes. ArVNDIVArs show bigger bathochromic shifts than HONDIVArs.


Mitral valve prolapse, panic disorder, and chest pain.
Mitral valve prolapse is a common cardiac disorder that can readily be diagnosed by characteristic auscultatory and echocardiographic criteria. Although many diseases have been associated with mitral valve prolapse, most affected individuals have the primary form of the disorder. Mitral valve prolapse is an inherited condition commonly associated with myxomatous degeneration of the mitral valve and its support structures. Complications of mitral valve prolapse, including cardiac arrhythmias, sudden death, infective endocarditis, severe mitral regurgitation (with or without chordae tendineae rupture), and cerebral ischemic events, occur infrequently considering the wide prevalence of the disorder. Panic disorder is a specific type of anxiety disorder characterized by at least three panic attacks within a 3-week period or one panic attack followed by fear of subsequent panic attacks for at least 1 month. It too is a common condition with a prevalence and age and gender distribution similar to that of mitral valve prolapse. Panic disorder and mitral valve prolapse share many nonspecific symptoms, including chest pain or discomfort, palpitations, dyspnea, effort intolerance, and pre-syncope. Chest pain is the symptom in both conditions that most commonly brings the patient to medical attention. The clinical description of chest pain in patients with mitral valve prolapse is highly variable, possibly reflecting multiple etiologies. Chest pain in panic disorder is usually characterized as atypical angina pectoris and as such bears resemblance to the chest pain commonly described by patients with mitral valve prolapse. Multiple investigative attempts to elucidate the mechanism of chest pain in both conditions have failed to identify a unifying cause. Review of the literature leaves little doubt that mitral valve prolapse and panic disorder frequently co-occur. Given the similarities in their symptomatology, a high rate of co-occurrence is, in fact, entirely predictable. There is, however, no convincing evidence of a cause-effect relationship between the two disorders, nor has a single pathophysiologic or biochemical mechanism been identified that unites these two common conditions. Until specific biologic markers for these disorders are identified, it may be impossible to do so. The lack of a proven cause-and-effect relationship between mitral valve prolapse and panic disorder and the absence of a unifying mechanism do not diminish the clinical significance of the high rate of co-occurrence between the two conditions. Primary care physicians and cardiologists frequently encounter patients with mitral valve prolapse and nonspecific symptoms with no discernible objective cause who fail to respond to beta-blockade. Panic disorder should be considered as a possible explanation for symptoms in such patients.(ABSTRACT TRUNCATED AT 400 WORDS)


Psychotropic Medications in Metabolic and Bariatric Surgery: Research Updates and Clinical Considerations.
We review evidence for assessing and monitoring psychotropic medications in metabolic and bariatric surgery (MBS) patients. We describe weight gain side effects, potential perioperative risks, pharmacokinetic changes that occur after MBS, and conclude with clinical recommendations. Research on psychiatric medication use and post-MBS weight outcomes is lacking and inconsistent; however, there is consistent evidence that, though variable, psychiatric medication use is associated with weight gain. Several meta-analyses and reviews provide guidance on lowering risk when appropriate. Perioperative lithium toxicity and SSRI discontinuation syndrome also warrant consideration, as do potential post-operative pharmacokinetic changes. In the absence of data for each psychiatric drug classification, close symptom monitoring and, where appropriate, serum concentration monitoring are recommended. MBS patients are a psychiatrically vulnerable population, and many are on psychiatric medications. Given potential weight/metabolic side effects, perioperative complications, and post-operative pharmacokinetic changes that occur with psychotropic medication use, providers should stay well informed on psychiatric medication management considerations.


Interactions of CD45-associated protein with the antigen receptor signaling machinery in T-lymphocytes.
CD45 is a transmembrane protein tyrosine phosphatase playing an essential role during T-cell activation. This function relates to the ability of CD45 to regulate p56(lck), a cytoplasmic protein tyrosine kinase necessary for T-cell antigen receptor (TCR) signaling. Previous studies have demonstrated that CD45 is constitutively associated in T-lymphocytes with a transmembrane molecule termed CD45-AP (or lymphocyte phosphatase-associated phosphoprotein). Even though the exact role of this polypeptide is unclear, recent analyses of mice lacking CD45-AP have indicated that its expression is also required for optimal T-cell activation. Herein, we wished to understand better the function of CD45-AP. The results of our studies showed that in T-cells, CD45-AP is part of a multimolecular complex that includes not only CD45, but also TCR, the CD4 and CD8 coreceptors, and p56(lck). The association of CD45-AP with TCR, CD4, and CD8 seemed to occur via the shared ability of these molecules to bind CD45. However, binding of CD45-AP to p56(lck) could take place in the absence of other lymphoid-specific components, suggesting that it can be direct. Structure-function analyses demonstrated that such an interaction was mediated by an acidic segment in the cytoplasmic region of CD45-AP and by the kinase domain of p56(lck). Interestingly, the ability of CD45-AP to interact with Lck in the absence of other lymphoid-specific molecules was proportional to the degree of catalytic activation of p56(lck). Together, these findings suggest that CD45-AP is an adaptor molecule involved in orchestrating interactions among components of the antigen receptor signaling machinery. Moreover, they raise the possibility that one of the functions of CD45-AP is to recognize activated Lck molecules and bring them into the vicinity of CD45.


Complications From Surgically Assisted Rapid Maxillary Expansion With HAAS and HYRAX Expanders.
The current study aimed at comparing the number and type of undesired outcomes during and after the maxillary expansion performed with HYRAX and HAAS expanders. A total of 90 patients (41 males and 49 females, 45.6% and 54.4%, respectively) aged 18 to 59 (mean age of 26.1; standard deviation [SD] = 7.4) underwent subtotal Le Fort I osteotomy and pterygomaxillary disjunction following surgically assisted rapid maxillary expansion (SARME) carried out using HAAS (n = 29; 48.3% male and 51.7% female; mean age = 27: SD = 7.7) and HYRAX (n = 61; 44.3% male and 55.7% female; mean age = 26; SD = 7.2) expanders. Post-SARME dento-gingival, radiographic, and clinical undesired outcomes were evaluated. A total of 16 (17.8%) patients experienced at least 1 undesired outcome-7 (7.8%) and 9 (10.0%) in HAAS and HYRAX group, respectively. The most common undesired outcomes were radiographic asymmetric expansion-2 (2.2%) and 3 (3.3%) in HAAS and HYRAX group, respectively-followed by pain during out-of-clinic expansion 4 (4.4%) in HAAS group only-dental darkening 5 (5.5%) in HYRAX group, only, requiring root canal treatment, and local infection-2 (2.2%), 1 in each HAAS and HYRAX groups. Excepting for complications arising from the acrylic stop plate in HAAS expander, the number and severity of complications observed in the current study did not differ due to the use of HAAS and HYRAX appliances to perform maxillary expansion. Hygiene issues do not rule out the use of HAAS. The wider maxillary expansion performed, the more frequent are the cases of asymmetric expansion.


Resistance in tuberculosis: what do we know and where can we go?
Tuberculosis (TB) has become a worldwide threat, mainly due to the emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis (Mtb). This mini-review is focused on the various mechanisms of resistance to the currently available anti-TB drugs and provides perspective on novel strategies and lead scaffolds/compounds aimed at inhibiting/overcoming these resistance mechanisms.


Structure-activity study of intact porcine motilin.
Biologically important sites on intact porcine motilin (pMTL) were explored using its partial peptides. The partial peptides were synthesized using Fmoc (9-fluorenylmethyloxycarbonyl) solid phase methodology, and tested for the binding activity to motilin receptor and the smooth muscle contractile activity. The results were as follows: important residues for the contractile activity were found to be Phe1, Ile4, and Tyr7, and an open space existed beyond the N-terminus between motilin and its receptor. On the model of interaction between motilin and motilin receptor evolved from these results, the three points of interaction, due to Phe1, Ile4, and Tyr7, and the presence of an open space were expected. The motilin agonist and antagonist, designed on this model, will help the inquiry into motilin associated diseases.


The Relationship Between Disproportionate Social Support and Metabolic and Inflammatory Markers: Moderating Role of Socioeconomic Context.
The present study examines the association of disproportionate social support (the relative balance of support given versus received) on metabolic and inflammatory outcomes and whether effects vary by socioeconomic context. We enrolled a sample of 307 parental caregivers living with a child with a chronic illness. Parents were assessed on four dimensions of social support: emotional support received, instrumental support received, emotional support given, and instrumental support given. Disproportionate social support was calculated as the difference between support received and support given. Participants provided sociodemographic information, were interviewed about financial stress, and were assessed on metabolic (systolic blood pressure, diastolic blood pressure, total cholesterol, body fat percent, and body mass index) and inflammatory (interleukin 6 and C-reactive protein) outcomes. More disproportionate instrumental and emotional support was associated with higher inflammation (b = 0.10, SE = 0.04, p = .014; b = 0.0.09, SE = 0.05, p = .042, respectively). We observed significant interactions between disproportionate social support and income (b = -0.04, SE = 0.02, p = .021). Parents from lower-income households who gave more emotional support than they received had higher inflammation compared with those from higher-income households. We also observed a significant interaction between disproportionate instrumental support and income (b = 0.04, SE = 0.02, p = .006). Parents from lower-income households who received more instrumental support than they gave had worse metabolic outcomes compared with parents from higher-income households. Parallel interaction patterns were observed using an interview-based measure of financial stress. These findings show that disproportionate social support has implications for physical health, particularly for caregivers from socioeconomically disadvantaged households.


New treatments for the motor symptoms of Parkinson's disease.
Levodopa remains the most potent drug to treat motor symptoms in Parkinson's disease (PD); however, motor fluctuations and levodopa-induced dyskinesia that occur with long-term use restrict some of its therapeutic value. Despite these limitations, the medical treatment of PD strives for continuous relief of symptoms using different strategies throughout the course of the illness: increasing the half-life of levodopa, using 'levodopa-sparing agents' and adding non-dopaminergic drugs. New options to 'improve' delivery of levodopa are under investigation, including long-acting levodopa, nasal inhalation and continuous subcutaneous or intrajejunal administration of levodopa. Long-acting dopamine agonists were recently developed and are undergoing further comparative studies to investigate potential superiority over the immediate-release formulations. Non-dopaminergic drugs acting on adenosine receptors, cholinergic, adrenergic, serotoninergic and glutamatergic pathways are newly developed and many are being evaluated in Phase II and Phase III trials. This article focuses on promising novel therapeutic approaches for the management of PD motor symptoms and motor complications. We will provide an update since 2011 on new formulations of current drugs, new drugs with promising results in Phase II and Phase III clinical trials, old drugs with new possibilities and some new potential strategies that are currently in Phase I and II of development (study start date may precede 2011 but are included as study is still ongoing or full data have not yet been published). Negative Phase II and Phase III clinical trials published since 2011 will also be briefly mentioned.


Dowry in 21st-century India: the sociocultural face of exploitation.
The World Health Organization (2009) implicates deep-rooted cultural and social norms as influential contributing factors toward physical and intimate partner violence against women. The dowry system is a social practice that perpetuates the oppression, torture, and murder of women in India. The practice of dowry is an expected part of marriage in cultures where arranged marriages are the norm. Violence can occur when the dowry or bride-price is deemed unsatisfactory by the recipient. In India, in spite of laws prohibiting the practice, not much has changed over the last 30 years. The National Crime Records Bureau of India, recorded a total of 8,618 female deaths related to dowry disputes in 2011, and the Asian Women's Human Rights Council (2009) estimates that the practice of dowry is implicated in 25,000 deaths and maiming of women between the ages of 15-34 in India every year. The current review of literature reveals that despite efforts on the part of the Indian government, social activists and feminists organizations in India, not much has changed over the past decade, in fact, the problem has increased, resulting in an unprecedented amount of mortality and morbidity among women in India.


CpGIF: an algorithm for the identification of CpG islands.
CpG islands (CGIs) play a fundamental role in genome analysis and annotation, and contribute to improving the accuracy of promoter prediction. Besides, CGIs in promoter regions are abnormally methylated in cancer cells and thus can be used as tumor markers. However, current methods for identifying CGIs suffer from various drawbacks. We present a new algorithm for detecting CGIs, called CpG Island Finder (CpGIF), which combines the best features in the most commonly used algorithms and avoids their disadvantages as much as possible. Five public tools for CpG island searching are used to compare with CpGIF for the assessment of accuracy and computational efficiency. The results reveal that CpGIF has higher performance coefficient and correlation coefficient than these previous methods, which indicates that CpGIF is able to provide high sensitivity and specificity at the same time. CpGIF is also faster than those methods with comparable prediction accuracy.


Orthostatic convulsive syncope in a burn patient.
Orthostatic convulsive syncope is defined as a decrease in cerebral blood supply resulting in convulsive, seizure-like symptoms. The authors present the first case report of orthostatic convulsive syncope in a burn patient. There are many causes of transient loss of consciousness in patients. An algorithm is presented to aid in the workup and management strategies for this diagnosis. This approach in conjunction with a neurology consult should add in the assessment and treatment of transient loss of consciousness and orthostatic convulsive syncope in a burn patient.


Echocardiographic characteristics of cardiac involvement in Systemic lupus erythematosus.
Echocardiography is a non invasive tool for the assessment of systemic lupus erythematesus (SLE) involvement . to investigate the cardiac involvement in patients diagnosed with SLE assessed by echocardiography and to study relationship between several factors and cardiac manifestation . retrospective study of 76 patients with diagnosis of SLE between 2008 and 2017. All patients were asssesed by echocardiography .Patients were assigned into cardiac abnormalities group and non cardiac abnormmalties and compared to study relations between several factors and cardiac manifestation . Cardiac involvement was found in echocardiography in 52% of patients (40 patients. Echocardiographic findings showed 12 cases ( 38 %) of pericardial effusion . Valvular abnormalities were observed in 19 cases (48 %), Myocardium was involved in 5 cases ( 12.5 %). there were no cases of myocarditis , High arterial pulmonary hypertension was reported in 4 cases (10%). Men were more vulnerable to cardiac involvement in lupus , there was signifiant relationship between disease duration and cardiac abnormalities (p 0.04 ), age was not associated significantly to echocardiographic abnormalites ,positif antiphospholipid antibodies(aPL+) was observed in higher frequency in cardiac involvement group with p<0.01 and especially in valvular anomalies Conclusion : Echocardiography should be routinely indicated for evaluation of cardiac involvement during SLE. These manifestations are most often moderate and asymptomatic. Pericardial effusion, and valvular involvement were the most frequent abnormalities.


Seasonal Variation in the Fecal Coliform Population of Louisiana Oysters and its Relationship to Microbiological Quality.
Seasonal variation was observed in the type of bacteria which comprised the fecal coliform population of oysters. Escherichia coli was the principal fecal coliform when water temperatures were below 22°C. Conversely, Klebsiella sp. predominated during the summer months. No significant relationship was observed between levels of E. coli and enterococci and non- E. coli fecal coliforms in oysters. Fecal coliform and E. coli levels were significantly (p >0.001) related in water. Klebsiella sp. isolated from oysters demonstrated considerably less multiple antimicrobial agent resistance than clinical isolates of K. pneumoniae . Fecal coliform-positive Klebsiella species had characteristics of environmental organisms. Results of this study suggest that high levels of non- E coli fecal coliforms in oysters harvested in the summer from beds meeting the fecal coliform water standard are not indicative of sewage pollution. Furthermore, it is suggested that the safety indicator in the guideline for oyster meats should be changed form fecal coliforms to E. coli .


Assessment of heavy metal pollution in stream sediments for the Baoji City section of the Weihe River in Northwest China.
The concentrations of Pb, Zn, Cu, Cd and Cr in the stream sediment in the Baoji City section of the Weihe River, Northwest China, were determined to evaluate their contamination levels, spatial distribution and potential ecological risk. The average concentrations of the heavy metal sediments were 52.92 mg kg(-1) for Pb, 99.04 mg kg(-1) for Zn, 17.43 mg kg(-1) for Cu, 0.79 mg kg(-1) for Cd and 86.97 mg kg(-1) for Cr. The result of the assessment indicates that the pollution by Cd is serious, Zn and Cr are moderate and Cu is relatively light or unpolluted. The correlation analysis showed that the five heavy metals are significantly associated with each other. The hierarchical cluster analysis suggested that Zn, Cr and Pb might have identical anthropogenic and natural sources in stream sediments while Cu and Cd might have the same source in the Baoji City section of the Weihe River.


Wavelength dispersion of optical fibers directly measured by ''difference method'' in the 0.8-1.6 microm range.
A novel technique to measure the wavelength dispersion of optical fibers in the 0.8-1.6 microm range, where germanium avalanche photodiodes possess adequate quantum efficiency, is described. Dispersion is defined as dtau/dlambda, which can safely be changed to the difference formula Deltatau/Deltalambda, when Deltalambda is small, where tau is the transit time of the wave and lambda is the light wavelength. A monochromatic light, whose amplitude is modulated by a sinusoidal baseband signal, is launched into the optical fiber. The phase of the sinusoidal baseband signal changes with the monochromatic light wavelength variation due to the dispersion of the fiber. The phase variation gives an accurate value of Deltatau. The wavelength dispersion is obtained directly from the values of both Deltatau and Deltalambda. Using this technique, the wavelength dispersion of a single mode optical fiber, for example, is measured in the single mode wavelength range from 0.92 to about 1.6 microm.


Swedish Council on Technology Assessment in Health Care (SBU). Chapter 8. Sick leave due to coronary artery disease or stroke.
The assessment of the literature on sick-leave with cardiovascular diseases include only studies with sufficient scientific quality. These studies describe sick leave following stroke, myocardial infarction, coronary artery bypass grafting (CABG), or percutaneous coronary intervention (PCI). We found limited scientific evidence for the following results: After stroke, more than half of the patients of working age returned to work (RTW) during the first year following onset (higher rate for the younger patients). The consequences of brain damage, e.g. impaired ADL ability or cognitive capacity, play an important role in this respect. Also after myocardial infarction most patients RTW. PCI is a milder coronary artery intervention than CABG and RTW is more rapid. However, in the long run there are no differences in sick leave. People at higher ages or with physically demanding jobs return to work to a lesser degree. An international comparison shows that the duration of sick leave due to these conditions in Sweden is longer than in other countries although there is no scientific evidence to support this practice. It appears that the interest in research on sick leave in patients with cardiovascular diseases has waned in recent years. Developments in acute cardiological care should inspire renewed scientific involvement in this area of research.


Hydrophobic folding units at protein-protein interfaces: implications to protein folding and to protein-protein association.
A hydrophobic folding unit cutting algorithm, originally developed for dissecting single-chain proteins, has been applied to a dataset of dissimilar two-chain protein-protein interfaces. Rather than consider each individual chain separately, the two-chain complex has been treated as a single chain. The two-chain parsing results presented in this work show hydrophobicity to be a critical attribute of two-state versus three-state protein-protein complexes. The hydrophobic folding units at the interfaces of two-state complexes suggest that the cooperative nature of the two-chain protein folding is the outcome of the hydrophobic effect, similar to its being the driving force in a single-chain folding. In analogy to the protein-folding process, the two-chain, two-state model complex may correspond to the formation of compact, hydrophobic nuclei. On the other hand, the three-state model complex involves binding of already folded monomers, similar to the association of the hydrophobic folding units within a single chain. The similarity between folding entities in protein cores and in two-state protein-protein interfaces, despite the absence of some chain connectivities in the latter, indicates that chain linkage does not necessarily affect the native conformation. This further substantiates the notion that tertiary, non-local interactions play a critical role in protein folding. These compact, hydrophobic, two-chain folding units, derived from structurally dissimilar protein-protein interfaces, provide a rich set of data useful in investigations of the role played by chain connectivity and by tertiary interactions in studies of binding and of folding. Since they are composed of non-contiguous pieces of protein backbones, they may also aid in defining folding nuclei.


Rapid detection of Mycobacterium tuberculosis in sputa by the amplification of IS6110.
A polymerase chain reaction (PCR) assay for the rapid detection of Mycobacterium tuberculosis in sputum samples was studied. The target DNA was a 123-base pair (bp) fragment of IS6110, which was repeated in the M.tuberculosis genome and was specific for the M.tuberculosis complex. Glass beads (2mm diameter) and lysozyme were used to lyse the mycobacteria and DNA was extracted by the phenol-extraction method. The amplified PCR product was detected by examination of ethidium-bromide-stained agarose gel and by hybridization with an oligonucleotide alkali-phosphatase-labeled probe. A total of 70 samples were tested. PCR was positive in all 13 smear and culture-positive samples, in 5 of 8 smear-negative and culture-positive samples, and in 1 of 49 smear and culture negative samples. The overall sensitivity and specificity were 85.7% and 98%, respectively. Thus, IS6110 as a PCR target was found to be very useful for the rapid diagnosis of M.tuberculosis infection and start of anti-tuberculous chemotherapy.


FoxO1 Is a Novel Regulator of 20S Proteasome Subunits Expression and Activity.
Proteostasis collapses during aging resulting, among other things, in the accumulation of damaged and aggregated proteins. The proteasome is the main cellular proteolytic system and plays a fundamental role in the maintenance of protein homeostasis. Our previous work has demonstrated that senescence and aging are related to a decline in proteasome content and activities, while its activation extends lifespan in vitro and in vivo in various species. However, the mechanisms underlying this age-related decline of proteasome function and the down-regulation in expression of its subunits remain largely unclear. Here, we demonstrate that the Forkhead box-O1 (FoxO1) transcription factor directly regulates the expression of a 20S proteasome catalytic subunit and, hence, proteasome activity. Specifically, we demonstrate that knockout of FoxO1, but not of FoxO3, in mice severely impairs proteasome activity in several tissues, while depletion of IRS1 enhances proteasome function. Importantly, we show that FoxO1 directly binds on the promoter region of the rate-limiting catalytic β5 proteasome subunit to regulate its expression. In summary, this study reveals the direct role of FoxO factors in the regulation of proteasome function and provides new insight into how FoxOs affect proteostasis and, in turn, longevity.


Impact of halides on the simultaneous separation of aromatic amines and their acidic metabolites by capillary electrophoresis with laser-induced native fluorescence detection under acidic conditions.
This paper describes a simple, sensitive, efficient, and rapid method for simultaneous analysis of biologically active amines and acids by capillary electrophoresis in conjunction with laser-induced native fluorescence detection (CE-LINF) using a diode pumped solid state nanolaser at 266 nm. In order to optimize resolution of the amines that were prepared in 10.0 mM formate-Tris (FT) solutions, 10.0 mM FT solutions with and without containing halides were used to fill the capillary and reservoirs, respectively. The electrophoretic mobilities of tryptamine (TA) and serotonin (5-HT) at pH 4.0 decrease with the increase in halide concentration (0-10.0 mM). Taken together with a great effect of iodide than other halides, we suggest that the formation of ion pairs is a main contributor for altering the migration of the amines. In order to simultaneously analyze the amines and their metabolites (acids) at low pH, a high bulk EOF is required. The analysis of 10 anlytes including amines and acids was completed within 12 min by CE-LINF using a capillary treated with 0.5M NaOH and then filled with 10.0 mM FT solutions (pH 4.0) containing 10.0 mM KCl prior to analysis. The limits of detection for TA and 5-hydroxyindole-3-acetic acid (5-HIAA) are 0.12 and 6.0 nM, respectively. The present method has been further validated by analyzing urine samples, with an RSD less than 3.1% (migration times) and 3.9% (concentration).


Intrastrain genomic and phenotypic variability of the commercial Saccharomyces cerevisiae strain Zymaflore VL1 reveals microevolutionary adaptation to vineyard environments.
The maintenance of microbial species in different environmental conditions is associated with adaptive microevolutionary changes that are shown here to occur within the descendants of the same strain in comparison with the commercial reference strain. However, scarce information is available regarding changes that occur among strain descendants during their persistence in nature. Herein we evaluate genome variations among four isolates of the commercial winemaking strain Saccharomyces cerevisiae Zymaflore VL1 that were re-isolated from vineyards surrounding wineries where this strain was applied during several years, in comparison with the commercial reference strain. Comparative genome hybridization showed amplification of 14 genes among the recovered isolates being related with mitosis, meiosis, lysine biosynthesis, galactose and asparagine catabolism, besides 9 Ty elements. The occurrence of microevolutionary changes was supported by DNA sequencing that revealed 339-427 SNPs and 12-62 indels. Phenotypic screening and metabolic profiles also distinguished the recovered isolates from the reference strain. We herein show that the transition from nutrient-rich musts to nutritionally scarce natural environments induces adaptive responses and microevolutionary changes promoted by Ty elements and by nucleotide polymorphisms that were not detected in the reference strain.


Hearing loss in children with mitochondrial disorders.
At least 1-5 children per 1000 suffer from congenital hearing loss, and 50% of these cases can be attributed to genetic causes. It has been estimated that 1% of pre-lingual hearing loss is due to mutations in mitochondrial DNA. Previous literature reports audiometric data for few patients, usually less than 20 per study. The goal of this study was to characterize the hearing loss associated with mitochondrial mutations and determine whether previously characterized patterns of hearing loss in these patients (progressive, sensorineural, high frequency losses) are found in our population as well. An IRB-approved retrospective chart review of the electronic medical records in the Nemours/Alfred I. dupont Hospital for Children system from January 2004 to October 2009 (a five-year period) was undertaken using ICD-9 codes 277.87 (mitochondrial disorder) and 359.89BA (mitochondrial myopathy). These 149 records were then evaluated for audiologic data, resulting in 26 charts with both a mitochondrial disorder and hearing evaluation. Of 26 patients with known mitochondrial disorders and audiometric documentation, 15 (58%) had hearing loss, and 11 patients had normal hearing (42%). Ten patients had sensorineural hearing loss (38%), two patients had conductive hearing loss (7.7%), one patient had a mixed hearing loss (3.8%), and two patients had an as yet undefined hearing loss (ABR had not yet been performed at the time of this study) (7.7%). In comparison with previous studies, generally including less than 20 patients, this is one of the largest collections of audiometric data on children with mitochondrial disorders. Unlike prior studies describing a progressive, sensorineural loss across all frequencies or mainly affecting high frequencies, the hearing loss in our patients was more variable including low frequency losses, mid-frequency losses, and conductive losses and was often not progressive or even improved. Our overall 38% rate of sensorineural hearing loss correlates well with previous case series; this study clearly justifies the use of routine audiometric screening in children with mitochondrial disorders, including use of ABR and OAEs as ASND can be seen in this population, as well as repeat testing over time to evaluate for progression.


KR-39038, a Novel GRK5 Inhibitor, Attenuates Cardiac Hypertrophy and Improves Cardiac Function in Heart Failure.
G protein-coupled receptor kinase 5 (GRK5) has been considered as a potential target for the treatment of heart failure as it has been reported to be an important regulator of pathological cardiac hypertrophy. To discover novel scaffolds that selectively inhibit GRK5, we have identified a novel small molecule inhibitor of GRK5, KR-39038 [7-((3-((4-((3-aminopropyl)amino)butyl)amino)propyl) amino)-2-(2-chlorophenyl)-6-fluoroquinazolin-4(3H)-one]. KR-39038 exhibited potent inhibitory activity (IC50 value=0.02 μM) against GRK5 and significantly inhibited angiotensin II-induced cellular hypertrophy and HDAC5 phosphorylation in neonatal cardiomyocytes. In the pressure overload-induced cardiac hypertrophy mouse model, the daily oral administration of KR-39038 (30 mg/kg) for 14 days showed a 43% reduction in the left ventricular weight. Besides, KR-39038 treatment (10 and 30 mg/kg/ day, p.o.) showed significant preservation of cardiac function and attenuation of myocardial remodeling in a rat model of chronic heart failure following coronary artery ligation. These results suggest that potent GRK5 inhibitor could effectively attenuate both cardiac hypertrophy and dysfunction in experimental heart failure, and KR-39038 may be useful as an effective GRK5 inhibitor for pharmaceutical applications.


A novel 3-d reconstruction system for the assessment of bifurcation lesions treated by the mini-crush technique.
Conventional two-dimensional angiography lacks the ability to properly image the true bifurcation geometry, and its percutaneous coronary intervention-induced changes in the clinical setting. A novel three-dimensional reconstruction system was investigated by retrospectively analyzing 39 lesions in 35 consecutive patients with coronary bifurcation disease treated with the mini-crush technique. At baseline, significant correlations were proved between two- and three-dimensional systems in terms of either reference vessel diameter (R(2)= 0.68 and 0.29 for main and side branches, respectively), minimum lumen diameter (R(2)= 0.73 and 0.36), stenosis diameter (R(2)= 0.69 and 0.29), and lesion length (R(2)= 0.48 and 0.58). These results were consistent with those observed after the procedure and at 8-month follow-up. Lesion length was significantly longer with the three-dimensional compared to the two-dimensional system for both main and side branches (P < 0.001, and P = 0.007, respectively). The three-dimensional quantitative reconstruction system may provide accurate evaluation of the complex curvilinear structure of bifurcation lesions when using a double stent technique.


How will surgical site infection be measured to ensure "high quality care for all"?
As of April 2010 all NHS institutions in the United Kingdom are required to publish data on surgical site infection, but the method for collecting this has not been decided. We examined 7448 trauma and orthopaedic surgical wounds made in patients staying for at least two nights between 2000 and 2008 at our institution and calculated the rate of surgical site infection using three definitions: the US Centers for Disease Control, the United Kingdom Nosocomial Infection National Surveillance Scheme and the ASEPSIS system. On the same series of wounds, the infection rate with outpatient follow-up according to Centre for Disease Control was 15.45%, according to the UK Nosocomial infection surveillance was 11.32%, and according to ASEPSIS was 8.79%. These figures highlight the necessity for all institutions to use the same method for diagnosing surgical site infection. If different methods are used, direct comparisons will be invalid and published rates of infection will be misleading.


Stroke volume and mitral annular velocities. Insights from tissue Doppler imaging.
The aim of this study was to assess the impact of stroke volume (SV) on mitral annular velocities derived from tissue Doppler imaging (TDI). To this end, conventional echocardiographic variables and TDI derived mitral annular velocities (S', E', A') were obtained in 14 patients (pts) with increased SV (due to primary mitral (n=12) (ISV group)), in 41 pts with reduced SV (due to ischemic (n=27) or dilated cardiomyopathy (n=9) or hypertensive heart disease (n=5) (RSV group)) and 29 asymptomatic controls with normal SV (CON group). Systolic (S') and early diastolic (E') mitral annular velocities were elevated in the ISV group in the comparison to the CON group, but were significantly reduced in the RSV group. Late diastolic annular velocities (A') did not differ between the ISV and the CON group, but were lowest in the RSV group. On simple linear regression analysis, SV was significantly related to S' (r=0.74, p<0.001), to E' (r=0.74, p<0.001) and to A' (r=0.43, p<0.01). On multiple regression analysis, SV was a stronger independent predictor of S' and E' than conventional systolic or diastolic echocardiographic variables. Thus, stroke volume has a significant impact on TDI derived systolic (S') and early diastolic (E') mitral annular velocities. This should be considered, when TDI is used in the evaluation of LV performance or in the estimation of filling pressures.


Mortality for sarcoidosis patients on the transplant wait list in the Lung Allocation Score era: Experience from a high volume center.
Sarcoidosis progresses to end stage fibrotic lung disease in 10% of patients and may necessitate lung transplantation. Organ allocation is currently determined by the Lung Allocation Score (LAS), but its performance in a sarcoidosis population has not been evaluated. To determine sarcoidosis-specific wait list mortality and identify predictive factors of death on the transplantation wait list. This was a single-center retrospective study of all sarcoidosis patients listed for lung transplant from March 2012 to February 2019. We compared patients who were transplanted to those who died awaiting organs. We collected baseline listing characteristics, physiologic testing, and outcomes data. Statistical analysis was performed by 2-tailed Student's t-test, Mann-Whitney U test, and Chi-Square analysis (where appropriate). Receiver-operating characteristic curves were constructed for variables reaching statistical significance. Twenty eight sarcoidosis patients were included in analysis. Mortality among wait listed patients was 18%, which exceeded the mortality of COPD and IPF. LAS scores did not differ at initial listing (41 vs. 46, p = 0.35) or at transplant/death (41 vs. 41, p = 0.91); wait list times also did not statistically differ (307 days vs. 177 days, p = 0.19). We identified bilirubin (AUC = 0.92), DLCO (AUC = 0.84), FEV1/FVC at transplant/death (AUC = 0.85), and composite physiologic index (AUC = 0.86) as predictors of death on the transplant list. Pulmonary hypertension was not associated with death. Unexpected sudden death was common in our cohort and was associated with markers of advanced fibrotic disease, not pulmonary hypertension.


Pharmacotherapy of pulmonary embolism.
Pulmonary embolism (PE) and deep vein thrombosis are common causes of illness and death. The pharmacological approach to pulmonary embolism includes the use of anticoagulants, unfractionated heparin for the acute phase, and oral anticoagulants for prophylaxis. In massive PE, the use of thrombolytic agents is suggested to reduce systemic hypotension and right ventricular failure and increase cardiac output. Thrombolytic agents act on pulmonary vascular obstruction. In clinical practice, thrombolytic therapy is recommended in case of massive embolism with haemodynamic failure. Recent studies suggest the use of thrombolytic drugs in patients with normal systemic blood pressure who show right ventricular dysfunction at echocardiographic examination. A large randomised trial on lytic agents in submassive PE is therefore needed. Anticoagulants were primarily indicated for prevention of recurrences. Due to the development of low molecular weight heparin, the role of anticoagulants needs to be re-evaluated.


Reversible antibiotic loading and pH-responsive release from polymer brushes on contact lenses for therapy and prevention of corneal infections.
Corneal infection is an important cause of corneal damage and vision loss. In this work, polyhydroxy antibiotics were grafted onto polymer brush-modified contact lenses through dynamic chemical bonds between polyphenolic hydroxyls and phenylboronic acid. Both in vitro and in vivo antibacterial tests demonstrated great promise in the prevention of bacterial keratitis, which could be attributed to the enhanced retention time and drug bioavailability.


Molecular virology of hepatitis C virus: an update with respect to potential antiviral targets.
Hepatitis C virus (HCV), a positive-strand enveloped RNA virus, is a major cause of chronic liver disease worldwide. Cis-acting RNA elements and virus-encoded polypeptides required for HCV replication represent attractive targets for the development of antiviral therapies. Internal ribosome entry site-directed translation of HCV genome RNA produces a long polyprotein which is co- and post-translationally processed to yield at least 10 viral proteins. A host signal peptidase is responsible for maturation of the structural proteins located in the N-terminal one-third of the polyprotein. Thus far, four enzymatic activities encoded by the non-structural (NS) proteins have been reported. The NS2-3 region encodes an autoproteinase responsible for cleavage at the 2/3 site. The N-terminal one-third of NS3 functions as the catalytic subunit of a serine proteinase which cleaves at the 3/4A, 4A/4B, 4B/5A and 5A/5B sites, and NS4A is an essential cofactor for some of these cleavages. NS3 also encodes an RNA-stimulated NTPase/RNA helicase at its C terminus, and NS5B has been shown to possess an RNA-dependent RNA polymerase activity. To date, no functions have been reported for NS4B or NS5A in RNA replication, however, NS5A has been implicated in modulating the sensitivity of HCV to interferon. Sequence and structural conservation within the 3' terminal 98 bases of genomic RNA suggest a functional importance in the virus life-cycle and hence another target for antiviral intervention. Recently, HCV infection was shown to be initiated in chimpanzees following intrahepatic inoculation of RNA transcribed from cloned HCV cDNA. The ability to generate large quantities of infectious HCV RNA may facilitate the development of reliable cell culture replication systems useful for the evaluation of antiviral drugs.


Probing osmotic effects on invertase with L-(-)-sucrose.
L-(-)-sucrose was efficiently synthesized using intramolecular aglycon delivery and used to elucidate osmotic effects on the activity of invertase, which catalyzes the hydrolysis of D-(+)-sucrose. The osmotic effect imposed by L-sucrose was responsible for more than 30% of the activity loss ascribed otherwise to "substrate inhibition."


Synthesis of unnatural amino acids functionalized with sterically shielded pyrroline nitroxides.
A series of unnatural amino acids functionalized with sterically shielded pyrroline nitroxides were synthesized. Their reduction by ascorbate/glutathione indicates that L-cysteine functionalized with gem-diethylpyrroline nitroxide is reduced at the slowest rate and is comparable to that measured for the most resistant to reduction pyrroline and pyrrolidine nitroxides.