Metabolic clearance rate and production rate of calcitriol in uremia.
We have previously demonstrated that while both normal humans and dogs tightly control serum calcitriol levels after 25(OH)D administration, anephric humans and 5/6 nephrectomized dogs significantly increase circulating 1,25(OH)2D when supraphysiological concentrations of 25(OH)D are reached in serum. Plasma 1,25(OH)2D level is determined not only by its rate of production but also by its rate of degradation. To further characterize the mechanisms involved in the responses to 25(OH)D therapy in normal circumstances and in chronic uremia, we measured metabolic clearance rate (MCR) and production rate (PR) of 1,25(OH)2D in normal dogs and in dogs with moderate and severe renal failure, at normal and supraphysiological serum concentrations of 25(OH)D. Basal MCR in uremic dogs, either with moderate or with severe renal failure, did not differ significantly from normals (6.7 +/- 0.7, 6.8 +/- 0.4 and 6.8 +/- 0.3 ml/min, respectively). Oral 25(OH)D administration for two weeks did not affect MCR either in normal animals or in both groups of uremic dogs. 25(OH)D treatment did not affect production rates in normal dogs and in animals with moderate renal failure (with normal basal values of 1,25(OH)2D), but significantly increased 1,25(OH)2D production from 0.13 +/- 0.01 to 0.25 +/- 0.04 micrograms/day (P less than 0.05) in dogs with severe renal insufficiency. These data suggest that it is the basal level of 1,25(OH)2D which regulates the synthesis of 1,25(OH)2D in response to 25(OH)D administration in normal and uremic animals.


Cisplatin-based chemotherapy in dysgerminoma of the ovary: thirteen-year experience at the Institut Gustave Roussy.
Twelve patients with dysgerminoma of the ovary were treated with various cisplatin-based chemotherapy regimens. Chemotherapy was delivered as primary postoperative treatment in 6 patients. All of them are free of disease 18 to 180 months after initiation of chemotherapy. Six other patients received chemotherapy as part of the salvage treatment for recurrent disease. Three failures were observed: one toxic death, one primary failure, and one subsequent relapse. Three patients remain free of disease 50 to 95 months after initiation of chemotherapy. The role of chemotherapy in early- and advanced-stage dysgerminoma of the ovary is reviewed.


A method for rapid machine learning development for data mining with doctor-in-the-loop.
Classifying free-text from historical databases into research-compatible formats is a barrier for clinicians undertaking audit and research projects. The aim of this study was to (a) develop interactive active machine-learning model training methodology using readily available software that was (b) easily adaptable to a wide range of natural language databases and allowed customised researcher-defined categories, and then (c) evaluate the accuracy and speed of this model for classifying free text from two unique and unrelated clinical notes into coded data. A user interface for medical experts to train and evaluate the algorithm was created. Data requiring coding in the form of two independent databases of free-text clinical notes, each of unique natural language structure. Medical experts defined categories relevant to research projects and performed 'label-train-evaluate' loops on the training data set. A separate dataset was used for validation, with the medical experts blinded to the label given by the algorithm. The first dataset was 32,034 death certificate records from Northern Territory Births Deaths and Marriages, which were coded into 3 categories: haemorrhagic stroke, ischaemic stroke or no stroke. The second dataset was 12,039 recorded episodes of aeromedical retrieval from two prehospital and retrieval services in Northern Territory, Australia, which were coded into 5 categories: medical, surgical, trauma, obstetric or psychiatric. For the first dataset, macro-accuracy of the algorithm was 94.7%. For the second dataset, macro-accuracy was 92.4%. The time taken to develop and train the algorithm was 124 minutes for the death certificate coding, and 144 minutes for the aeromedical retrieval coding. This machine-learning training method was able to classify free-text clinical notes quickly and accurately from two different health datasets into categories of relevance to clinicians undertaking health service research.


Magnetic resonance imaging phase encoding: a pictorial essay.
A set of MRI images with various degrees of phase encoding were generated from the same raw data set. The resultant pictorial teaching aid is useful in developing an intuitive understanding of the mechanics and principles of phase encoding in two dimensional, Fourier transform magnetic resonance imaging.


Metabolic engineering of rice leading to biosynthesis of glycinebetaine and tolerance to salt and cold.
Genetically engineered rice (Oryza sativa L.) with the ability to synthesize glycinebetaine was established by introducing the codA gene for choline oxidase from the soil bacterium Arthrobacter globiformis. Levels of glycinebetaine were as high as 1 and 5 micromol per gram fresh weight of leaves in two types of transgenic plant in which choline oxidase was targeted to the chloroplasts (ChlCOD plants) and to the cytosol (CytCOD plants), respectively. Although treatment with 0.15 M NaCl [corrected] inhibited the growth of both wild-type and transgenic plants, the transgenic plants began to grow again at the normal rate after a significantly less time than the wild-type plants after elimination of the salt stress. Inactivation of photosynthesis, used as a measure of cellular damage, indicated that ChlCOD plants were more tolerant than CytCOD plants to photoinhibition under salt stress and low-temperature stress. These results indicated that the subcellular compartmentalization of the biosynthesis of glycinebetaine was a critical element in the efficient enhancement of tolerance to stress in the engineered plants.


Pulsed electric fields for selection of hematopoietic cells and depletion of tumor cell contaminants.
Purging of tumor cells and selection of stem cells are key technologies for enabling stem cell transplantation and stem cell gene therapy. Here we report a strategy for cell selection based on physical properties of the cells. Exposing cells to an external pulsed electric field (PEF) increases the natural potential difference across the cell membrane until a critical threshold is reached and pore formation occurs, resulting in fatal perturbation of cell physiology. Attaining this threshold is a function of the applied field intensity and cell size, with larger cells porated at lower field intensities than smaller cells. Since hematopoietic stem cells are smaller than other hematopoietic cells and tumor cells, we found that exposure of peripheral blood mononuclear cells (PBMCs) to PEFs caused stepwise elimination of monocytes without affecting the function of smaller lymphocyte populations. Mobilized peripheral blood exposed to PEFs was enriched for CD34+/CD38- cells and stem cell function was preserved. Furthermore, PEF treatment was able to selectively purge blood preparations of tumor cells and eradicate transplantable tumor.


Genome-wide analysis and metabolic profiling unveil the role of peroxidase CsGPX3 in theaflavin production in black tea processing.
Plucked tea leaves can be processed into black tea (Camellia sinensis), which is rich in health-promoting molecules, including flavonoid antioxidants. During black tea processing, theaflavins (TFs) and thearubigins (TRs) are generated via the successive oxidation of catechins by endogenous polyphenol oxidase (PPO)- or peroxidase (POD)-mediated reactions. This process must be well controlled to achieve the proper TF/TR ratio, which is an important quality parameter of the tea beverage. However, little is known about the POD/PPO catalyzed TF formation process at the molecular genetic level. Here, we identified and characterized the POD genes responsible for TF production in tea. Genome-wide analysis of POD/PPO family genes, metabolite profiling, and expression analysis of PPO/POD genes in tea leaves enabled us to select several PPO/POD genes potentially involved in TF production. Differential gene expression in plant tissues and enzyme activity in several tea varieties traditionally used for processing of various beverage types indicate that black tea processing primarily depends on PPO/POD activity. Among these POD/PPO genes, the POD CsGPX3 is involved in the generation of TFs during black tea processing. The capacity of PPO/POD-catalysed TF production is potentially used for controlling catechin oxidation during black tea processing and could be used to create molecular markers for breeding of tea plant varieties suitable for the production of high-quality black tea beverages.


Refractory Ventricular Fibrillation Treated with Double Simultaneous Defibrillation: Pilot Study.
Refractory shockable rhythm has a high mortality rate and poor neurological outcome. Treatments for refractory shockable rhythm presenting after defibrillation and medical treatment are not definite. We conducted research on the application of double simultaneous defibrillation (DSiD) for refractory shockable rhythms. This is a retrospective pilot study performed using medical records from 1 January 2016 to 31 December 2017. The prephase was from January to December 2016. The post-phase was from January to December 2017. During the prephase, we conducted conventional defibrillation with one defibrillator, and during the post-phase, we conducted DSiD using two defibrillators. Primary outcome was survival to hospital discharge. Secondary outcomes included survival to hospital admission and good neurological outcome at 12 months. Statistical analysis was conducted using Fisher's exact test. Data were regarded statistically significant when p < 0.05. A total of 38 patients were included. Twenty-one patients underwent conventional defibrillation, and 17 underwent DSiD. The DSiD group had a higher survival to admission rate (14/17 (82.4%) vs. 6/21 (28.6%), p=0.001) and showed a trend for higher survival to discharge (7/17 (41.2%) vs. 3/21 (14.3%), p=0.078). Good neurological outcome at 12 months of the DSiD group was higher than that of the conventional defibrillation group, but the difference was not statistically significant (5/17 (29.4%) vs 2/21 (9.5%), p=0.207). In patients with refractory shockable rhythms, DSiD has increased survival to hospital admission and a trend of increased survival to hospital discharge. However, DSiD did not improve neurological outcome at 12 months.


Author response to: Cardiovascular risk factors in offspring exposed to gestational diabetes mellitus in utero: systematic review and meta-analysis.
This commentary is an author response to Yu and colleagues regarding the manuscript entitled 'Cardiovascular risk factors in offspring exposed to gestational diabetes mellitus in utero: Systematic review and meta-analysis'. We address their concern regarding minor errors in our manuscript, our search strategy and assessment of heterogeneity.


Synthesis, characterization, cytotoxicity and DNA binding studies of diamminediethyldithiocarbamato-platinum(II) nitrate.
A new complex [Pt(NH3)2(ddtc)]NO3.2H2O as a 1:1 electrolyte has been prepared. This was characterized by spectroscopic methods. The electronic absorption spectrum of this complex in water suggests that it has a square planar geometry. The infrared, 1H NMR and x-ray photoelectron spectroscopic studies suggest the bonding of ammonia molecules and diethyldithiocarbamate as bidentate ligand to platinum(II) in this complex. The 50% inhibition value of this complex against P388 lymphocytic leukemia cells is comparable with cisplatin. This complex interacts with calf thymus DNA by coordinate covalent bond.


Medications and patient safety in the trauma setting: a systematic review.
Medication errors account for the most common adverse events and a significant cause of mortality in the USA. The Joint Commission has required medication reconciliation since 2006. We aimed to survey the literature and determine the challenges and effectiveness of medication reconciliation in the trauma patient population. We conducted a systematic review of the literature to determine the effectiveness of medication reconciliation in trauma patients. English language articles were retrieved from PubMed/Medline, CINAHL, and Cochrane Review databases with search terms "trauma OR injury, AND medication reconciliation OR med rec OR med rek, AND effectiveness OR errors OR intervention OR improvements." The search resulted in 82 articles. After screening for relevance and duplicates, the 43 remaining were further reviewed, and only four articles, which presented results on medication reconciliation in 3041 trauma patients, were included. Two were retrospective and two were prospective. Two showed only 4% accuracy at time of admission with 48% of medication reconciliations having at least one medication discrepancy. There were major differences across the studies prohibiting comparative statistical analysis. Trauma medication reconciliation is important because of the potential for adverse outcomes given the emergent nature of the illness. The few articles published at this time on medication reconciliation in trauma suggest poor accuracy. Numerous strategies have been implemented in general medicine to improve its accuracy, but these have not yet been studied in trauma. This topic is an important but unrecognized area of research in this field.


Breeding phenology, variation in reproductive effort and offspring size in a tropical population of the woodlouse Porcellionides pruinosus.
Most species of woodlice in temperate habitats have discrete breeding seasons. It is hypothesised that breeding synchronises with favourable environmental conditions to maximise offspring growth and survivorship (Willows 1984). We measured the breeding phenology of a species introduced to a tropical environment, primarily to consider the assumption that life histories in the tropics will differ fundamentally from those in temperate habitats. In addition to breeding phenology we considered variation in reproductive effort between individual females and the division of this effort between the size and number of young.A continuous breeding phenology was observed in a synanthropic population of Porcellionides pruinosus within the tropics. Reproductive effort varied between months, showed a weak relationship with female size and was independent of female fecundity. Female sizefecundity relationships varied between samples and when the proportion of reproductive females was high size-fecundity slopes were steeper than at other times. Mean offspring size varied between months and there was a wide range in offspring size within broods. Offspring size was not related to female body mass, reproductive effort or fecundity; consequently brood mass increased linearly with an increase in fecundity. Increased reproductive effort goes into more rather than larger offspring.We propose that the continuous breeding in this population was the result of the constant presence of an environmental cue to reproduction evolved in temperate habitats. Continuous breeding is not necessarily equivocal to high individual reproductive success even though overall population growth may be rapid. However, variation in reproductive effort suggests that individuals respond to current environmental conditions on short time scales.


Cerebellar involvement associated with immune checkpoint inhibitors: A systematic review.
Immune checkpoint inhibitors (ICIs) targeting programmed death receptor 1 (PD-1), cytotoxic T-lymphocyte-associated-4 (CTLA-4) and programmed cell death ligand 1 can be associated with immune-related adverse events (iRAEs). Amongst neurological iRAEs, cerebellar involvement seems to be rare and currently lacks a proper characterization. The aim of this study was to phenotype cerebellar iRAEs. A systematic review was performed according to PRISMA guidelines including reported patients with cerebellar involvement related to ICIs and with available individual data. After screening 2765 records, 32 studies with 46 patients were included. Median age was 63 years (20-82), and most patients were male (63.0%). Isolated cerebellitis was observed in 32.6% of cases, whilst the remaining cases had "cerebellitis plus", mostly associated with encephalitis/encephalopathy. Associated tumors included most frequently lung cancer, melanoma and Merkel cell carcinoma. PD-1 inhibitor was the most administered treatment (n = 29, 64.4%), whilst exposure to CTLA-4 inhibitor was rare (n = 2, 4.5%). Magnetic resonance imaging was abnormal in 43.2% of patients and inflammatory cerebrospinal fluid findings were frequently observed. Autoantibodies were detected in 61.9% of patients and included novel reactivities. Amongst treatment strategies, the most common were steroids (n = 36) and ICI discontinuation (n = 28, 90.3%). Relapses were reported in 10% of patients. Most patients showed improvement/remission (n = 31) but, at last follow-up, 12 had died. Isolated cerebellitis versus cerebellitis-plus differed in terms of outcomes, whilst seropositive versus seronegative patients had distinct tumor associations. Cerebellar iRAEs are usually multifocal, have heterogeneous tumor associations, are most associated with PD-1 inhibitor exposure and are related to autoantibodies, including novel reactivities.


Improvement of mortality rate and decrease in histologic hepatic injury after human cord blood stem cell infusion in a murine model of hepatotoxicity.
Because of their plasticity potential local and systemic application of cord blood stem cells may represent excellent candidates for cell-based therapeutic strategies in toxic liver injuries. It is already known that intraperitoneal administration of hematopoietic stem cells provides rapid liver homing in animal models of hepatic injury. We sought to assess the efficacy of a hematopoietic stem cell infusion to decrease the histologic damage and the mortality rate of animals previously damaged by allyl alcohol. NOD/SCID mice were divided into two groups. (1) animals treated by intraperitoneal administration of allyl alcohol and (2) animals treated with allyl alcohol and 24 hours later with an intraperitoneal infusion of human cord blood cells. Flow cytometry, histology, immunohistochemistry, and RT-PCR were performed to monitor human cell engraftment by evidences of human hepatic markers. Human stem cells were able to transdifferentiate into hepatocytes, improve liver regeneration after damage, and reduce the mortality rate even when requiring qualitative and quantitative differences in the transdifferentiation processes. The mortality rate decreased from 70% to 20%, with a significant improvement in the histologic findings. We demonstrated that the infusion of hematopoietic stem cells into the liver in the early stage of damage might initiate endogenous hepatic tissue regeneration that oppose the injury inflicted by toxicants.


'Inflammatory' abdominal aortic aneurysms.
The term 'inflammatory aneurysm' is used to describe a variant of atherosclerotic abdominal aortic aneurysms in which the wall of the aneurysm is unusually thick and surrounded by extensive fibrosis and adhesions. Repair of these aneurysms is associated with a higher mortality and morbidity than repair of those which are non-inflammatory, so that diagnosis prior to surgery is desirable. The use of computed tomography (CT) and ultrasound in this differentiation is discussed. The correct diagnosis was made in 16 out of 17 by CT, but in only three of nine cases who had ultrasound scans.


Altered hemoglobin-oxygen affinity with long-term propranolol therapy in patients with coronary artery disease.
Pharmacologic agents that alter hemoglobin affinity for oxygen may affect systemic or myocardial oxygen delivery. In vitro, and in normal man propranolol shifts the oxyhemoglobin equilibrium curve to the right, thus increasing the partial pressure of oxygen at which hemoglobin is 50% saturated (P50) and enhancing oxygen delivery. The effect of propranolol on hemoglobin P50 was evaluated in 12 patients with angina pectoris and documented coronary artery disease. Determinations were made during oral propranolol therapy (mean daily dose 152 mg) of at least 3 months' duration and after administration of propranolol had been discontinued for at least 4 days. Hemoglobin P50 and erythrocyte 2,3-diphosphoglycerate (DPG) were measured. Data in 12 patients were: the mean P50 after discontinuation of propranolol was 28.2 mm Hg+/-0.9 (standard error of the mean) and during propranolol therapy 31.7+/-0.7; P less than 0.001; red blood cell 2,3-DPG did not change to explain the increase in P50. This demonstrated shift could increase systemic oxygen delivery and thus benefit marginally perfused myocardium while sparing coronary flow. Propranolol, in addition to its negative chronotropic and inotropic effects, may increase tissue oxygen delivery in patients with the anginal syndrome.


Low-dose radiotherapy effects the progression of anti-tumor response.
The history of low-dose radiotherapy (LDRT or LDR) as a treatment modality for malignant tumors dates back to the 1920s. Even with the minimal total dose administered during treatment, LDRT can result in long-lasting remission. Autocrine and paracrine signaling are widely recognized for fostering the growth and development of tumor cells. LDRT exerts systemic anti-tumor effects through various mechanisms, such as enhancing the activity of immune cells and cytokines, shifting the immune response towards an anti-tumor phenotype, influencing gene expression, and blocking crucial immunosuppressive pathways. Additionally, LDRT has been demonstrated to enhance the infiltration of activated T cells and initiate a series of inflammatory processes while modulating the tumor microenvironment. In this context, the objective of receiving radiation is not to directly kill tumor cells but to reprogram the immune system. Enhancing anti-tumor immunity may be a critical mechanism by which LDRT plays a role in cancer suppression. Therefore, this review primarily focuses on the clinical and preclinical efficacy of LDRT in combination with other anti-cancer strategies, such as the interaction between LDRT and the tumor microenvironment, and the remodeling of the immune system.


The role of claudins in homeostasis.
Sequential expression of claudins, a family of tight junction proteins, along the nephron mirrors the sequential expression of ion channels and transporters. Only by the interplay of transcellular and paracellular transport can the kidney efficiently maintain electrolyte and water homeostasis in an organism. Although channel and transporter defects have long been known to perturb homeostasis, the contribution of individual tight junction proteins has been less clear. Over the past two decades, the regulation and dysregulation of claudins have been intensively studied in the gastrointestinal tract. Claudin expression patterns have, for instance, been found to be affected in infection and inflammation, or in cancer. In the kidney, a deeper understanding of the causes as well as the effects of claudin expression alterations is only just emerging. Little is known about hormonal control of the paracellular pathway along the nephron, effects of cytokines on renal claudin expression or relevance of changes in paracellular permeability to the outcome in any of the major kidney diseases. By summarizing current findings on the role of specific claudins in maintaining electrolyte and water homeostasis, this Review aims to stimulate investigations on claudins as prognostic markers or as druggable targets in kidney disease.


Actions of kainate and AMPA selective glutamate receptor ligands on nociceptive processing in the spinal cord.
Kainate receptors expressing the GluR5 subunit of glutamate receptor are present at high levels on small diameter primary afferent neurones that are considered to mediate nociceptive inputs. This suggests that GluR5 selective ligands could be novel analgesic agents. The role of kainate receptors on C fibre primary afferents has therefore been probed using three compounds that are selective for homomeric GluR5 receptors. The agonist, ATPA, and the antagonists, LY294486 and LY382884, have been tested in four models of nociception: responses evoked by noxious stimulation of the periphery have been recorded electrophysiologically (1) from hemisected spinal cords from neonatal rats in vitro, (2) from single motor units in adult rats in vivo, (3) from dorsal horn neurones in adult rats in vivo, and (4) in hotplate tests with conscious mice. In some protocols comparisons were made with the AMPA selective antagonist GYKI 53655. The agonist ATPA reduced nociceptive reflexes in vitro, but failed to have effects in vivo. In all tests, the GluR5 antagonists reduced nociceptive responses but only at doses that also affected responses to exogenous AMPA. The AMPA antagonist reduced nociceptive responses at doses causing relatively greater reductions of responses to exogenous AMPA. The results indicate that GluR5 selective ligands do reduce spinal nociceptive responses, but they are not strongly analgesic under these conditions of acute nociception.


Effects of Pasteurella haemolytica A1 leukotoxin on bovine neutrophils: degranulation and generation of oxygen-derived free radicals.
To further define the role of Pasteurella haemolytica A1 leukotoxin in the pathogenesis of bovine pneumonic pasteurellosis, its in vitro effects on bovine neutrophils were investigated. Leukotoxin-containing culture supernatant, from P. haemolytica, stimulated a neutrophil respiratory burst as measured by the generation of oxygen-derived free radicals O2- and H2O2. This effect was immediate because preincubation of neutrophils with the culture supernatant for 5 min or longer substantially suppressed this respiratory burst. This suppression was due to cytolysis of the neutrophils. Prolonged incubation of neutrophils with the same culture supernatant caused further cytolysis and degranulation. Heat-inactivated P. haemolytica culture supernatant that had lost its cytotoxic properties failed to stimulate respiratory burst by neutrophils. Furthermore, the respiratory burst, cytolysis and degranulation were abrogated only by leukotoxin-neutralizing monoclonal and polyclonal antibodies, but not by antibodies against the lipopolysaccharide. These studies show that the leukotoxin component in the culture supernatant was responsible for the generation of oxygen-derived free radicals and proteolytic enzymes from neutrophils which may participate in direct lung injury.


Comparison of Approved Dosages for Pediatric and Adult Populations Based on US Labeling Information.
The passing of legislation in the United States and the European Union has led to the approval of dosages for pediatric use. This study was conducted in an attempt to find potentially important factors with regard to dose selection for the pediatric population. The FDA's New Pediatric Labeling Information Database was used for this study. Drug labels for patients aged 6 months as well as those for patients aged 2, 6, and 11 years were standardized based on dosages expressed by age, normalized body weight (BW), and body surface area (BSA) in order to obtain ratios of pediatric-to-adult dosages. Labeling for 108 drugs were extracted for the analysis. Ratios of pediatric-to-adult dosages based on BW were higher than 1, but those based on BSA were around 1. Relative dosages at 6 months of age showed a stronger correlation with those at 2 years compared to those at other ages. The approved dosages for pediatrics based on BW were higher than those of adults, but the ones based on BSA were almost the same as those of adults. The closer the age groups, the stronger the correlation of relative dosages between the groups.


Sensitivity and specificity of surveillance case definitions in detection of influenza and respiratory syncytial virus among hospitalized patients, New Zealand, 2012-2016.
The WHO is exploring the value of adding RSV testing to existing influenza surveillance systems to inform RSV control programs. We evaluate the usefulness of four commonly used influenza surveillance case-definitions for influenza and RSV surveillance. SHIVERS, a multi-institutional collaboration, conducted surveillance for influenza and RSV in four New Zealand hospitals. Nurses reviewed admission logs, enrolled patients with suspected acute respiratory infections (ARI), and obtained nasopharyngeal swabs for RT-PCR. We compared the performance characteristics for identifying laboratory-confirmed influenza and RSV severe acute respiratory infection (SARI), defined as persons admitted with measured or reported fever and cough within 10 days of illness, to three other case definitions: 1. reported fever and cough or shortness of breath, 2. cough and shortness of breath, or 3. cough. During April-September 2012-2016, SHIVERS identified 16,055 admissions with ARI; of 6374 cases consented and tested for influenza or RSV, 5437 (85%) had SARI and 937 (15%) did not. SARI had the highest specificity in detecting influenza (40.6%) and RSV (40.8%) but the lowest sensitivity (influenza 78.8%, RSV 60.3%) among patients of all ages. Cough or shortness of breath had the highest sensitivity (influenza 99.3%, RSV 99.9%) but the lowest specificity (influenza 1.6%, RSV 1.9%). SARI sensitivity among children aged <3 months was 60.8% for influenza and 43.6% for RSV-both lower than in other age groups. While SARI had the highest specificity, its sensitivity was limited, especially among children aged <3 months. Cough or shortness of breath was the most sensitive.


microRNA hsa-miR-425-5p and hsa-miR-4523 expressions as biomarkers of active pulmonary tuberculosis, latent tuberculosis infection, and lymph node tuberculosis.
Studies on miRNA highlight its significance as an immunomarker for several diseases, including tuberculosis. This study aimed to determine the difference between miR-425-5p and miR-4523 expressions in patients with active pulmonary TB (PTB), latent TB infection (LTBI), and lymph node TB (LNTB), whose diagnosis remains challenging. This case-control study was performed on blood samples obtained from 23 patients with PTB, 21 with LTBI, 21 with LNTB, and 25 healthy controls (HC). miRNA hsa-miR-425-5p and hsa-miR-4523 expression levels were measured by RT-qPCR. Statistical analyses were performed using SPSS version 25.0. RT-qPCR showed that hsa-mir-425-5p and hsa-mir-4523 expression levels were significantly different among the four groups (PTB, LTBI, LNTB, and HCs). The hsa-mir-425-5p miRNA expression level in LNTB was higher than that in LTBI (p = 0.003). Meanwhile, the hsa-mir-4523 miRNA expression was downregulated in PTB and LNTB than in LTBI (p < 0.0001 and p = 0.015, respectively). The ROC analysis of a single sample showed that only mir-4523 could discriminate LTBI and HCs, with an AUC of 0.829 (p < 0.001). The ROC curve of each miRNA was further analyzed after logistic regression by adjusting for sex and age. The combination of both miRNAs was also analyzed. The model that analyzed the combination of both miRNAs after adjusting for age had the best performance in differentiating LNTB from LTBI, with an AUC of 0.97 (p < 0.001). miRNA hsa-mir-425-5p was upregulated and miRNA hsa-mir-4523 was downregulated in PTB and LNTB than in LTBI.


Restriction molecules involved in the interaction of human T cell clones with antigen-presenting cells.
Two of three distinct human Ia molecules detected by murine monoclonal antibodies (MoAb) have been suggested to be involved in antigen presentation for T cell responses to purified protein derivatives (PPD) and herpes simplex virus (HSV). This observation was first suggested from studies on the inhibition of proliferative responses of whole T cell populations with MoAb against human Ia molecules. To determine whether a single T cell recognizes the antigen in the context of both Ia molecules or in the context of each one of two Ia molecules, we isolated and propagated PPD-reactive T cell clones from an HLA-DR heterozygous individual. They showed four different restriction patterns: type I and type II clones each appeared to be restricted to one of two HLA-DR antigens, type III clone gave anomalous patterns of response and seemed to be restricted to non-DR antigens, and type IV clone recognized antigen when both DR antigens were presented on the same antigen-presenting cells (APC) surface. Blocking study with monoclonal anti-Ia antibodies suggested that type I, II and IV clones are restricted to DR molecules and type III clones are restricted to 1B4 molecules distinct from DR or MB1 molecules. These data imply that human T cell clones recognizing PPD in the context of each one of two Ia molecules are clonally distributed.


Diabetic peripheral neuropathy: role of reactive oxygen and nitrogen species.
The prevalence of diabetes has reached epidemic proportions. There are two forms of diabetes: type 1 diabetes mellitus is due to auto-immune-mediated destruction of pancreatic β-cells resulting in absolute insulin deficiency and type 2 diabetes mellitus is due to reduced insulin secretion and or insulin resistance. Both forms of diabetes are characterized by chronic hyperglycemia, leading to the development of diabetic peripheral neuropathy (DPN) and microvascular pathology. DPN is characterized by enhanced or reduced thermal, chemical, and mechanical pain sensitivities. In the long-term, DPN results in peripheral nerve damage and accounts for a substantial number of non-traumatic lower-limb amputations. This review will address the mechanisms, especially the role of reactive oxygen and nitrogen species in the development and progression of DPN.


Testicular toxicity of di-(2-ethylhexyl)phthalate in young Sprague-Dawley rats.
Di-(2-ethylhexyl)phthalate (DEHP), used widely in the manufacture of plastics, is a well-known reproductive toxicant. It causes apoptosis and loss of spermatogenic cells, resulting in testicular atrophy. Reports are scarce in the literature on the progression of apoptosis following repeated doses of phthalates. DEHP's mechanism of inducing testicular atrophy has been associated with depletion of zinc in the testis. ZnT-1 is a zinc transporter that is highly expressed in the testis. Thus, DEHP might exert its toxic effects on the testis by altering the expression of ZnT-1. In this regard, 25-day old Sprague-Dawley rats were given vehicle (5 ml corn-oil/kg, po) for 2, 7 and 14 days, or DEHP (2 g/5 ml corn-oil/kg, po) daily, for 1, 2, 3, 5, 7, 10 and 14 days. Zinc content in testes was determined by atomic absorption spectrophotometry, and ZnT-1 mRNA was quantified by the branched DNA signal amplification method. Body weight gain and testicular weight (absolute and relative) were significantly lower in DEHP-treated rats. DEHP produced morphological changes in the testis, including apoptosis, necrosis, and loss of spermatogenic cells, which resulted in testicular atrophy. Apoptotic index (AI: the percentage of apoptotic cells in seminiferous tubules), determined using the TUNEL technique, was markedly increased after 1 day (AI: 2.9%, control AI: 0.1-0.3%) followed by a peak at 3 days (AI: 11.5%) and a gradual decrease till 10-14 days (AI: 7-9%). Zinc content in testis was not changed 1 day after DEHP administration, but decreased significantly at later time points. No difference was found in ZnT-1 mRNA expression between control and DEHP-treated animals until day 14. Our results suggest that apoptosis, along with necrosis, plays an important role in the mechanism of testicular atrophy by DEHP. In addition, ZnT-1 mRNA expression was not altered by DEHP and therefore, it appears that ZnT-1 cannot account for the decrease in testicular Zn content. Pathological lesions and apoptosis occurred prior to the loss of zinc in testis, suggesting that zinc depletion might be a secondary effect of DEHP-induced testicular toxicity, rather than the cause.


Assessment of lipoedema awareness among polish women- online survey study.
Lipoedema is an adipose tissue disorder that is still not fully understood. The primary purpose of this study is to explore the state of knowledge and understanding of lipoedema among Polish women. The secondary aim is to investigate the possible association between knowledge and factors such as BMI, self-reported symptoms, and age. One hundred seventy polish women took part in an online survey study that was posted to social media groups and forums in January 2022. The survey consisted of 12 questions and aimed at assessing the basic knowledge about lipoedema. The least proportion of participants (4%) could correctly indicate the methods of lipoedema treatment. The accurate definition of lipoedema was indicated only by 7% of women, 12% identified characteristic features of lipoedema, and 37% correctly evaluated lipoedema curability. The greatest proportion of respondents knew the differences between obesity and lipoedema (50%). Awareness of lipoedema among women is deficient. A significant proportion of the respondents report the occurrence of lipoedema symptoms. In order to improve the situation of lipoedema patients, it is crucial to increase the knowledge about this condition both among medical professionals and the general public.


Effect of medical insurance and family financial risk on healthcare utilisation by patients with chronic diseases in China: a cross-sectional study.
To assess the joint cumulative effects of medical insurance and family health financial risk on healthcare utilisation among patients with chronic conditions in China. A nationwide population-based case-control study with multinomial logistic regression was conducted and used to estimate the ORs of healthcare utilisation against type of medical insurance and family health financial risk using the Anderson model as a theoretical framework. China Family Panel Studies (CFPS) database. The study sample included 5260 patients with chronic conditions identified from the 2014 CFPS database. The participants were classified by their health insurance coverage: urban employee basic medical insurance (UEBMI), Gong Fei Medical Insurance (GFMI), new rural cooperative medical scheme (NCMS) and urban residents basic medical insurance. Healthcare utilisation was measured by assessing the care level provided by the health institutions selected by patients when they were sick. Health financial risk was measured using the cost of medical expenditures and annual family income over the past year. Patients were more likely to choose hospital care than care from primary health centres. Patients with NCMS preferred primary healthcare, compared with patients with no medical insurance (OR 1.852, 95% CI 1.458 to 2.352). Patients with UEBMI and GFMI made use of hospital healthcare services (OR 2.654, 95% CI 1.85 to 3.81; OR 1.629, 95% CI 1.15 to 2.30, respectively). Patients who had medium or high financial risk were more likely to choose tertiary/specialised hospital care, compared with those at low financial risk (OR 1.629, 95% CI 1.15 to 2.30; OR 1.220, 95% CI 1.04 to 1.43, respectively). The majority of patients chose hospital care in our sample. There was a joint effect and relationship between degree of family health financial risk and medical insurance on healthcare utilisation.


Slab-selective, BOLD-corrected VASO at 7 Tesla provides measures of cerebral blood volume reactivity with high signal-to-noise ratio.
MRI methods sensitive to functional changes in cerebral blood volume (CBV) may map neural activity with better spatial specificity than standard functional MRI (fMRI) methods based on blood oxygen level dependent (BOLD) effect. The purpose of this study was to develop and investigate a vascular space occupancy (VASO) method with high sensitivity to CBV changes for use in human brain at 7 Tesla (T). To apply 7T VASO, several high-field-specific obstacles must be overcome, e.g., low contrast-to-noise ratio (CNR) due to convergence of blood and tissue T1 , increased functional BOLD signal change contamination, and radiofrequency field inhomogeneities. In the present method, CNR was increased by keeping stationary tissue magnetization in a steady-state different from flowing blood, using slice-selective saturation pulses. Interleaved acquisition of BOLD and VASO signals allowed correction for BOLD contamination. During visual stimulation, a relative CBV change of 28% ± 5% was measured, confined to gray matter in the occipital lobe with high sensitivity. By carefully considering all the challenges of high-field VASO and filling behavior of the relevant vasculature, the proposed method can detect and quantify CBV changes with high CNR in human brain at 7T.


The effect of RNA secondary structure on the action of a nucleolar endoribonuclease.
The effect of the folded macromolecular structure of RNA on the action of a purified single strand specific nucleolar ribonuclease was studied by comparing the limited hydrolysis of defined RNA substrates. The nucleolar RNase was shown to attack only single-stranded regions of the native 5.8 S rRNA, consistent with a computer-derived model for the secondary structure (Nazar, R. N., Stitz, T. O., and Busch, H. (1975) J. Biol. Chem. 250, 8591-8597). The single strand specific nucleolar RNase, unlike S1 nuclease, does not release the end-labeled nucleotide and therefore provides a more useful probe for structural analysis at or near 3'- or 5'-terminal ends of an RNA molecule. Although attacking only single strand regions of the native 5.8 S rRNA, the selectivity of the nucleolar RNase, when compared to S1 nuclease, is distinct and supports the suggestion that other factors besides the proposed secondary structure must also influence nuclease attack. The selective and limited attack of the nucleolar RNase on native RNA was similarly observed using mouse 45 S preribosomal RNA as a substrate and possibly suggests a role for this nucleolar RNase in ribosomal RNA processing.


[Criteria for assessing the relative and specific activity of insecticides].
Relative activity of chemicals and their specific activity coefficients are suggested as the criteria for comparative assessment of insecticidal properties of substances. Values of the afore-mentioned parameters of 34 chemicals compared to a standard are presented for 3 insect species: red cockroaches, house flies and bed-bugs.


Contact allergy to a cyclohexanone resin in humans and guinea pigs.
5 patients with allergic contact dermatitis caused by various paints were demonstrated to be sensitive to a cyclohexanone resin (C-R) present in the paints. Sensitization studies in guinea pigs with C-R and cyclohexanone showed one batch of C-R to be a sensitizer.


An integrative analysis of transcriptome-wide association study and mRNA expression profile identified candidate genes for attention-deficit/hyperactivity disorder.
Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder, but the genetic mechanism of ADHD remains elusive now. Tissue specific transcriptome-wide association study (TWAS) of ADHD was performed by FUSION utilizing a genome-wide association study (GWAS) dataset of ADHD (including 20,183 ADHD cases and 35,191 healthy controls) and gene expression reference from brain and blood. Furthermore, the genes identified by TWAS were compared with the differently expressed genes detected by mRNA expression profiles of ADHD rat model and autism spectrum disorders (ASD) patients. Functional enrichment and annotation analysis of the identified genes were performed by DAVID and FUMAGWAS tool. For brain tissue, TWAS identified 148 genes with P value < 0.05, such as TDO2 (PTWAS=4.01×10-2), CHD1L (PTWAS=9.64×10-3) and KIAA0319L (PTWAS=4.05×10-4). Further 11 common genes were examined in the mRNA expression datasets, such as ACSM5 (PTWAS=3.62×10-2, PmRNA=0.005), CCDC24 (PTWAS=1.49×10-2, PmRNA=2.35×10-3) and MVP (PTWAS=5.55×10-3, PmRNA=5.40×10-3). Pathway enrichment analysis of the genes identified by TWAS detected 3 pathways for ADHD, including Other glycan degradation (P value=0.021), Viral myocarditis (P value=0.034) and Endocytosis (P value=0.041). Through integrating GWAS and mRNA expression data, we identified a group of ADHD-associated genes and pathways, providing novel clues for understanding the genetic mechanism of ADHD.


A Quantitative Live-Cell Superresolution Imaging Framework for Measuring the Mobility of Single Molecules at Sites of Virus Assembly.
The insurgence of superresolution microscopy into the fields of virology and microbiology has begun to enable the mapping of molecular assemblies critical for host-pathogen interfaces that organize on a scale below the resolution limit of the light microscope. It is, however, challenging to completely understand the molecular interactions between host and pathogen from strictly time-invariant observations. Herein, we describe a method using simultaneous dual-color superresolution microscopy to gain both structural and dynamic information about HIV-1 assembly. Specifically, we demonstrate the reconstruction of single virus assembly sites using live-cell photo-activated localization microscopy (PALM) while concurrently assessing the sub-viral mobility of the HIV-1 envelope glycoprotein during interaction with the viral lattice. We propose that our method is broadly applicable to elucidating pathogen and host protein-protein interactions through quantification of the dynamics of these proteins at the nanoscale.


N-Oxide derivatives of 3-(3-pyridyl)-2-phosphonopropanoic acids as potential inhibitors of Rab geranylgeranylation.
The N-oxide derivatives of [2-(3-pyridinyl)-1-hydroxyethylidene-1,1-phosphonocarboxylic acid (or PEHPC) and [2-(3-pyridinyl)-1-ethylidene-1,1-phosphonocarboxylic acid (or PEPC) have been prepared and evaluated for their activity against several enzymes which utilize isoprenoids. The parent pyridines are known inhibitors of GGTase II, but the N-oxide derivatives show no improvement in biological activity in assays with the isolated enzyme. However, the PEHPC N-oxide did induce significant accumulation of intracellular light chain in myeloma cells, consistent with inhibition of Rab geranylgeranylation.


People's Response to Disaster: A Population Based Study of the Victims of 2018 Flood in Kerala, South India.
Natural disasters cause much hardship and suffering, loss of property, and increased morbidity and mortality amongst those affected. Timely and effective response for relief and rescue services go a long way in mitigating these consequences. This population-based cross-sectional, descriptive study conducted in the immediate aftermath of the catastrophic flood that occurred in Kerala, South India, in 2018, documents the experiences of the victims, the community's preparedness, and response to the disaster. Flood waters reached levels of over four feet within the premises of 55% of the houses and nearly 97% had water flooding inside their homes. More than 93% of the households were evacuated to safer locations and relief camps. The elderly and those with chronic illnesses were the worst sufferers, unable to access medical aid. Many families (62%) received help from neighbors. However, the loss of lives was minimal, and could be attributed to the immediate response of the local community in rescue and relief work. This experience underscores the vital importance of the local community as first responders, and their preparedness for disasters.


Appropriate prevention and detection of gastrointestinal neoplasms in the elderly.
The incidence of colorectal carcinoma and gastric cancer is related to environmental factors and lifestyle. Long-term exposure to multiple mutagens is believed to initiate the carcinogenesis of colorectal and gastric cancer. Even though patients older than 65 years of age have developed particular modes of cooking and dietary preferences, these habits can be changed with instruction, patient-doctor rapport, and suggestions of alternative foodstuffs that are palatable to them. Elderly patients can be persuaded to avoid fatty foods; smoked, pickled, and salted fish; and red meat. They should be encouraged to eat chicken, fish, fresh fruit, and vegetables (especially cruciferous vegetables), to ingest vitamin C, and to avoid overcooking, frying, and excessive broiling of meat and fish. Surveillance examinations must be practiced in the elderly to avoid malignant conversion of adenomatous polyps. All patients who have undergone gastric resections for peptic ulcer disease need to be watched carefully, with identification of high-risk individuals who must undergo periodic endoscopy.


Understanding the conservation patterns and molecular phylogenetics of human death receptors family through computational biology.
Human death receptors (TNFR1, FAS, DR3, DR4, DR5, DR6 and TNFBR), primarily from tumor necrosis receptor super family, play an essential role in the process of the extrinsic pathway of apoptosis. We performed conserved domain, amino acid residues analysis in which cysteine residues were found to be highly conserved for all the family members. Sixteen (16) highly conserved residues were observed in TNFR1, DR3 and TNFBR; and in case of Fas, only seven (7) residues are highly conserved. From molecular phylogenetics, we found that DR5 and DR4, TNFR1 and DR3 and TNFR1 and DR3 had the same point of origin. Alternatively, Fas was found to be distant from the rest of the death receptors. A network map was developed to explain these proteins are not only interlinked among themselves, but also interlinked with several other proteins. We have also observed from this system that scores of all the nodes ranges from 0.996 to 0.999.


Growth characteristics and eicosapentaenoic acid production by Nannochloropsis sp. in mixotrophic conditions.
Nannochloropsis sp. was grown under mixotrophic conditions with 30 mM glucose as carbon source, reaching 507 mg dry wt l(-1) after 8 d. This was 1.4-fold of that obtained under photoautotrophic conditions. Under mixotrophic and photoautotrophic cultivations, the net photosynthetic rate of Nannochloropsis sp. did not change but the respiratory rate increased in the mixotrophic cultivation. The yield of eicosapentaenoic acid was 22 mg l(-1) in the mixotrophic cultivation and 20 mg l(-1) under the photoautotrophic cultivation.


A comparative study of enzymatic and immunological parameters in Planorbarius corneus and Biomphalaria glabrata exposed to the organophosphate chlorpyrifos.
This study aimed to investigate the acute effects of chlorpyrifos on biomarkers related to neurotoxicity and immunotoxicity in two allopatric freshwater gastropod species belonging to the family Planorbidae. For this purpose, Planorbarius corneus and Biomphalaria glabrata were exposed to chlorpyrifos (active ingredient or commercial formulation) for 48 h at environmentally realistic concentrations (1 and 7.5 μg L-1). Basal acetylcholinesterase activity in soft tissues and hemolymph was almost one order of magnitude higher in P. corneus than in B. glabrata. However, upon chlorpyrifos exposure, statistically significant inhibition of enzymatic activity was registered in both species. Acetylcholinesterase was more sensitive to inhibition in soft tissues than in hemolymph. The highest inhibition was observed in the B. glabrata soft tissues exposed to the commercial formulation (88 % at 1 μg L-1 and 93 % at 7.5 μg L-1). Hemocyte number and lysosomal membrane stability did not show significant changes with respect to controls in any of the exposed groups. Superoxide anion generation was diminished (21-46 %) in P. corneus hemocytes exposed to the active ingredient and in B. glabrata hemocytes exposed to the active ingredient or the formulation. In contrast, hemocyte phagocytic activity increased in all exposed groups. Phagocytosis was most stimulated (89 %) in hemocytes sampled from B. glabrata treated with 7.5 μg L-1 chlorpyrifos. Altogether the results suggest that the freshwater gastropods P. corneus and B. glabrata are suitable model animals for environmental monitoring studies in the Northern Hemisphere and Latin America, respectively. Furthermore, these results add information on the relevance of testing pesticide formulations and on the usefulness of acetylcholinesterase inhibition and immunological parameters as biomarkers of the acute effects of chlorpyrifos in these species.


Neurorrhaphy of the recurrent laryngeal nerve.
The authors have experimentally performed neurorrhaphy and its modifications and nerve grafting with end-to-end anastomosis of the recurrent laryngeal nerve in dogs. Recovery of a neurorrhaphy of the recurrent laryngeal nerve resulted in the bizarre and spasmodic movement of the vocal cords. These effects were recorded by means of electromyography and 16 mm cinematography to demonstrate restoration of nerve muscle function and vocal cord movements. From these results, it was concluded that these single modes were not adequate for restoration of laryngeal function, however, some specific attention is given to a few trophic changes of the affected muscles after a period of ten months postoperative.


Comparative Risk of Hypophosphatemia Following the Administration of Intravenous Iron Formulations: A Network Meta-Analysis.
Intravenous iron therapy is increasingly used in patients with iron deficiency anemia, although concerns of hypophosphatemia have been recently raised. The aim of this study was to evaluate different intravenous iron formulations for the risk of hypophosphatemia. Medline, Scopus, Cochrane Central Register of Controlled Trials, Web of Science, Clinicaltrials.gov, and Google Scholar databases were systematically searched to 20 March 2020. All randomized controlled trials reporting the incidence of hypophosphatemia among adult patients treated with any intravenous iron preparation were included. Pool estimates were obtained by applying an arm-based Bayesian network meta-analysis model. Eight randomized controlled trials were included, comprising 5989 patients. Ferric carboxymaltose was associated with significantly higher incidence of hypophosphatemia compared to iron isomaltoside (risk ratio [RR]: 7.90, 95% confidence interval [CI]: 2.10-28.0), iron sucrose (RR: 9.40, 95% CI: 2.30-33.0), iron dextran (RR: 6.60, 95% CI: 1.91-220.0), and ferumoxytol (RR: 24.0, 95% CI: 2.50-220.0). Therefore, ferric carboxymaltose ranked as the worst treatment presenting the highest surface under the cumulative ranking curve (99.1%). No significant differences were estimated for the comparisons among iron isomaltoside, iron sucrose, iron dextran, and ferumoxytol. In conclusion, it is suggested that the occurrence of hypophosphatemia is common after the administration of intravenous ferric carboxymaltose. Further research is needed in large-scale randomized controlled trials to determine the risk of symptomatic and persistent hypophosphatemia as well as to elucidate the exact pathophysiology of the observed association.


Prediction of RDS from amniotic fluid analysis: a comparison of the prognostic value of TLC and infra-red spectroscopy.
Infra-red (IR) spectroscopy was recently shown to be a sensitive method for the determination of fetal lung maturity (Liu et al., 1998). The present study was undertaken to validate the newly developed method for prediction of RDS (Respiratory Distress Syndrome). Samples of amniotic fluid were obtained by amniocentesis from 86 patients between the 28th and 41st week of pregnancy. A small volume, 35 microliters, of amniotic fluid was used to acquire infra-red spectra with a commercial spectrometer. The lecithin/sphingomyelin (L/S) ratio was determined separately by TLC (thin layer chromatography). A calibration model was established using a partial least squares regression analysis which quantitatively correlated 145 IR spectra with the TLC-based L/S ratios; the correlation coefficient was 0.95. The model was then validated using a total of 111 spectra which also showed a high correlation coefficient (r = 0.91). Based upon the clinical data associated with these samples, the prediction accuracy for the presence of RDS was 67 per cent for TLC and 83.3 per cent for IR. The accuracy for predicting the absence of RDS was 93.4 per cent for TLC and 96.8 per cent for IR. We conclude that IR spectroscopy has the potential to become the clinical method of choice for predicting RDS from amniotic fluid analysis.


Pseudohyperaldosteronism from liquorice-containing laxatives.
Four cases of pseudohyperaldosteronism due to chronic ingestion of liquorice-containing laxatives are described. All patients had hypertension and hypokalemia with suppression of plasma renin activity and aldosterone; the diagnosis was based only on retrospective grounds. In patients with hypokalemia and hypertension a possibility of such a cause must be excluded to avoid unnecessary diagnostic procedures.


Family history of premature myocardial infarction, life course socioeconomic position and coronary heart disease mortality--A Cohort of Norway (CONOR) study.
To investigate self-reported family history (FH) of premature myocardial infarction (MI) in first-degree relatives as a risk factor for coronary heart disease (CHD) mortality, and assess whether any observed effect could be explained by current or life course socioeconomic position. 130,066 participants from Cohort of Norway were examined during 1994-2003. A subgroup (n=84,631) had additional life course socioeconomic data. Using Cox proportional hazard analyses, we calculated hazard ratios (HR) for CHD mortality, assessed by linkages to the Norwegian Cause of Death Registry through 2009. For subgroup analyses, we created an index of life course socioeconomic position, and assessed its role as a potential confounder in the association of FH with CHD. For men, MI in parents and siblings were both a significant risk factor for CHD mortality after adjusting for established risk factors and current socioeconomic conditions; the highest risk was with MI in siblings (HR: 1.44 [1.19-1.75]). For women, FH constituted significant risk after similar adjustment only for those with MI in parents plus siblings (HR: 1.78 [1.16-2.73]). Adjusting for current and life course socioeconomic conditions only marginally lowered the estimates, and those with FH did not have worse life course socioeconomic position than those without. FH of premature MI is an independent risk factor for CHD mortality that differs in magnitude of effect by the sex of the index person and type of familial relationship. Life course socioeconomic position has little impact on the association between FH and CHD, suggesting the effect is not confounded by this.


A supersensitive dot-hybridization method: rapid and quantitative detection of host-derived DNA in recombinant products at the one picogram level.
We have developed a highly sensitive method of DNA dot-blotting hybridization to detect host-derived DNA (nuclear DNA and plasmid DNA) in a recombinant product. This method has two distinctive features compared to the conventional hybridization method: firstly, a highly specific radioactive probe is prepared by using ultrasonicated DNA, instead of untreated DNA, as a template for the oligo-labeling reaction; secondly, the signal to noise ratio is increased by the use of lambda phage DNA as non-homologous DNA. This method enabled us to detect host-derived DNA at the one picogram level without using a radioisotope of high specific activity and long exposure times.


Synchronized, mass-emergences of a yucca moth, Prodoxus Y-inversus (Lepidoptera: Prodoxidae), after 16 and 17 years in diapause.
In 1985 and 1986, more than 180 adults of Prodoxus y-inversus Riley eclosed from cocoons of the 1969 generation in Yucca baccata, after prepupal larvae spent 16 and 17 years in diapause, intervals prior to mass emergence that are unmatched by any other insect on record. The emergences, which occurred during 15- to 16-day periods, followed many years of virtually no maturation by other individuals of the colony, and the size of the moths was not diminished by the long wait. Successful delay of development and synchronous emergence by many individuals indicates that whole populations can postpone activities through long periods of conditions that would be adverse for adult activity.


Carcinogenic, ethanol, acetaldehyde and noncarcinogenic higher alcohols, esters, and methanol compounds found in traditional alcoholic beverages. A risk assessment approach.
Greek fermentation and distillation industries produce traditional spirit beverages, such as tsipouro and tsikoudia, consumed both in bottles and bulk quantities by the general population or tourists. The same spirits are also produced by individuals at home since previous centuries, as a part of the local culture but mainly due to the Greek agricultural sector unique characteristics (small cultivation areas with great number of farmers). In this study, the concentrations of carcinogenic compounds: ethanol and acetaldehyde; and noncarcinogenic: higher alcohols (1-propanol, isobutanol, and isoamyl alcohol), esters (ethyl acetate), and methanol were measured to estimate the potential cancer risk and daily intake of these compounds. The margin of exposure (MOE) of carcinogenic compounds was found to be less than 500 (mean value), well below the toxic threshold of 10,000, above which there is not public concern, as suggested by the European Food Safety Authority. Additionally, through risk assessment of noncarcinogenic compounds, we identified two specific compounds in-bulk spirits (produced by individuals), namely ethyl acetate and isobutanol, with health risk index (HRI) greater than 1 (indicating a possibility to induce side effects by consumption of high amounts). Our results indicate that bottled spirits, which are produced in a controlled environment (alcohol industries), showed higher human safety level in terms of both carcinogenic and noncarcinogenic risk assessment studies, comparing to bulk beverages produced by individuals (with out strict regulations).


Transportal versus all-inside techniques of anterior cruciate ligament reconstruction: a systematic review.
Transportal (TP) and all-inside techniques (AIT) are the most commonly used anterior cruciate ligament (ACL) reconstruction procedures in current clinical practice. However, there is an ongoing debate over which procedure is superior. Therefore, the purpose of this systematic review was to evaluate and compare the clinical outcomes and complications of these two techniques to propose recommendations for future application. Our primary hypothesis was that AIT is a superior ACLR technique compared to TP. A systematic literature review, using PRISMA guidelines, was conducted using PubMed, Medline, Google Scholar, and EMBASE, up to February 2021 to identify studies focusing on AIT and TP techniques of ACL reconstruction. We excluded animal experiments, cadaveric studies, retrospective studies, case reports, technical notes, and studies without quantitative data. Patients' characteristics, surgical technical features, along with postoperative follow-up and complications were extracted and reported accordingly. Methodological quality of the included studies was assessed using the Modified Coleman Methodology Score (MCMS). A total of 44 studies were selected for this review, of which four were comparative studies. A total of 923 patients underwent AIT and 1678 patients underwent the TP technique for ACLR. A single semitendinosus graft was commonly used in the AIT compard to combined semitendinosus and gracilis graft in the TP group. The postoperative increase in International Knee Documentation Committee (IKDC), Lysholm, KT-1000, and Short Form-12 (physical and mental) scores were similar in the AIT group and the TP group. Contrastingly, the VAS pain score was significantly lower in the AIT group compared to the TP group. Furthermore, the pooled complication rates from all studies were similar between the two groups (AIT: 54 patients, 8.26% vs. PT: 55 patients, 6.62%). However, the four studies that prospectively compared AIT and TP techniques showed lesser complications in the AIT group than the TP group. Since the future trend in orthopedic surgery is toward less invasive and patients' satisfaction with good outcomes, AIT is a good alternative method considering preserving bony tissue and gracilis tendon with less post-operative pain, along with more knee flexor strength and equal outcomes compared to conventional ACL reconstruction surgery. Level of Evidence II.


Bidirectional chemotherapy combining intraperitoneal docetaxel with intravenous 5-fluorouracil and oxaliplatin for patients with unresectable peritoneal metastasis from gastric cancer: the first study in Western countries.
A new treatment using bidirectional intraperitoneal (IP) and intravenous (IV) chemotherapy developed by Asiatic surgeons improves outcomes in patients with synchronous peritoneal metastasis (PM) from gastric cancer (GC). We enrolled six consecutive patients with unresectable PM from GC who underwent bidirectional chemotherapy using IP docetaxel and IV FOLFOX or LV5FU2. In one course, IP docetaxel 30 mg/m2 was administrated on days 1, 8 and 15, and IV FOLFOX or LV5FU2 was administered on days 1 and 15, followed by 7 days of rest. Before and after a complete bidirectional cycle of three courses, the peritoneal cancer index (PCI) was evaluated by laparoscopy. The primary endpoint was to evaluate the feasibility and safety of bidirectional chemotherapy. Secondary endpoints were overall survival (OS), and the success of the therapeutic strategy was reflected by a decrease of 25% of the initial PCI. All patients completed one bidirectional cycle. The regimen was well tolerated. The median OS was 13 months [range 5-18], and the 1-year OS rate was 67%. After the first bidirectional cycle, the PCI decrease ≥25% of the initial value in four patients. A major histological response was observed in four patients. This is the first Western study and confirms the feasibility and safety of bidirectional treatment using IP and IV chemotherapy for patients with unresectable PM from GC, resulting in a 13-month median OS with limited morbidity. The decrease in PCI after one bidirectional cycle is promising.


Completeness of the circle of Willis and risk of ischemic stroke in patients without cerebrovascular disease.
We investigated circle of Willis (CoW) completeness in relation to the risk of future ischemic stroke in patients without prior cerebrovascular disease. We included 976 patients with atherosclerotic disease, but no previous TIA/stroke, from the Second Manifestations of ARTerial disease (SMART) study. All patients underwent MR angiography of the CoW. Cox regression was used to determine whether anterior CoW completeness (anterior communicating artery or A1 segments) and posterior CoW completeness (posterior communicating arteries or P1 segments) were related to future stroke, and whether CoW completeness influenced the relation between internal carotid artery (ICA) stenosis/occlusion and future stroke. Thirty patients (3.1 %) had ischemic stroke after 9.2 ± 3.0 years of follow-up. Twenty-four patients (80 %) had anterior circulation stroke. An incomplete anterior CoW was related to future anterior circulation stroke (HR 2.8 (95 % CI 1.3-6.3); p = 0.01), whereas a one-sided and two-sided incomplete posterior CoW were not (HR 2.2 (95 % CI 0.7-7.1; p = 0.19) and 1.9 (95 % CI 0.6-5.9; p = 0.29), respectively). In stratified analyses, patients with an incomplete anterior CoW had the highest risk of future anterior circulation stroke when they also had a one-sided (HR 7.0 (95 % CI 1.3-38.2; p = 0.02)) or two-sided incomplete posterior CoW (HR 5.4 (95 % CI 1.0-27.8; p = 0.04). CoW completeness did not change the relation between asymptomatic ICA stenosis/occlusion and future ischemic stroke (p = 0.68). An incomplete anterior CoW combined with an incomplete posterior CoW is related to future anterior circulation stroke. CoW completeness has no large effect on the relation between asymptomatic ICA stenosis/occlusion and future stroke.


Inter-hospital variation in data collection, radiotherapy treatment, and survival in patients with head and neck cancer: A multisite study.
Inter-hospital inequalities in head and neck cancer (HNC) survival may exist due to variation in radiotherapy treatment-related factors. This study investigated inter-hospital variation in data collection, primary radiotherapy treatment, and survival in HNC patients from an Australian setting. Data collected in oncology information systems (OIS) from seven Australian hospitals was extracted for 3,182 adults treated with curative radiotherapy, with or without surgery or chemotherapy, for primary, non-metastatic squamous cell carcinoma of the head and neck (2000-2017). Death data was sourced from the National Death Index using record linkage. Multivariable Cox regression was used to assess the association between survival and hospital. Inter-hospital variation in data collection, primary radiotherapy dose, and five-year HNC-related death was detected. Completion of eleven fields ranged from 66%-98%. Primary radiotherapy treated Tis-T1N0 glottic and any stage oral cavity and oropharynx cancers received significantly different time-corrected biologically equivalent dose in two gray fractions (EQD2T) by hospital, with observed deviation from Australian radiotherapy guidelines. Increased EQD2T dose was associated with a reduced risk of five-year HNC-related death in all patients and those treated with primary radiotherapy. Hospital, tumour site, and T and N classification were also identified as independent prognostic factors for five-year HNC-related death in all patients treated with radiotherapy. Unexplained variation exists in HNC-related death in patients treated at Australian hospitals. Available routinely collected data in OIS are insufficient to explain variation in survival. Innovative data collection, extraction, and classification practices are needed to inform clinical practice.


Lumbosacral chordoma metastatic to the eyelid.
The authors report a patient treated with radiation therapy for a lumbosacral chordoma. The first and only evidence of metastatic disease was an eyelid cyst. This case is unusual for several reasons. First, eyelid metastases are rare; they are much more uncommon than metastases to the uvea or orbit. Second, metastatic tumors to the eyelid are usually manifestations of widespread disease and seldom occur as a solitary focus of dissemination. Third, the clinical presentation of our patient's lesion as an eyelid cyst is uncommon for a metastasis to the eyelid. Finally, to the best of our knowledge, all previously reported tumors metastatic to the eyelid have been carcinomas; this is the first report of a metastatic soft-tissue tumor to the eyelid.


Volumetric assessment of airborne indoor and outdoor fungi at poultry and cattle houses in the Mazandaran Province, Iran.
The aim of this study was to assess the volume of airborne fungi in the indoor and outdoor environment of poultry and cattle houses in the Mazandaran Province in Iran. Indoor and outdoor air of twenty cattle houses and twenty-five poultry houses were sampled using a single-stage impactor, which draws air at 20 L min-1 and impacts sampled material onto Petri plates containing malt extract agar. The plates were incubated at 30 °C for seven days, after which the resulting colonies were counted. The fungi were identified and counted microscopically and macroscopically. A total of 4,662 fungal colonies were isolated from 90 plates collected from indoor and outdoor air of cattle and poultry houses. Cladosporium (55.3 %), yeast (10.0 %), and Aspergillus (9.4 %) were the most common findings. The concentration of airborne fungi in cattle and poultry houses ranged from 10 CFU m-3 to 1700 CFU m-3 in indoor and 10 CFU m-3 to 2170 CFU m-3 in outdoor environments. Cladosporium had the highest mean indoor (424.5 CFU m-3) and outdoor (449.7 CFU m-3) air concentration in the cattle houses. In the poultry houses, the highest mean concentrations were measured for Cladosporium (551.0 CFU m-3) outdoors and yeast (440.7 CFU m-3) indoors. These levels might present an occupational risk, but threshold levels for these environments have yet to be established worldwide.


A double-blind comparison of the new ibuprofen-codeine phosphate combination, zomepirac, and placebo in the relief of postepisiotomy pain.
In a double-blind, single-dose study, the analgesic effect of a combined ibuprofen-codeine phosphate preparation was compared with those of zomepirac and placebo in 127 patients with moderate or severe postepisiotomy pain. Both the combination and zomepirac were significantly more effective than placebo for up to six hours, but the onset of action of the combination was more rapid than that of zomepirac. The study was notable for the virtual absence of side effects.


Metagenomic analysis for detecting pathogens in culture-negative infective endocarditis.
Pathogen identification is important for proper diagnosis and optimal treatment of infective endocarditis (IE). Blood and valve cultures are the gold standard for detecting pathogens responsible for IE. However, these tests only detect culturable pathogens, and have low sensitivity, especially in patients previously treated with antibiotics. Culture-negative IE is still a major clinical problem and a diagnostic challenge. Recently, metagenomic analysis using next generation sequencing has been used to detect pathogens directly from clinical samples. However, there are very few reports of the use of metagenomic analysis for pathogen identification in culture-negative IE cases and the usefulness of this new method is unknown. Here, we report a case of successful pathogen detection with metagenomic analysis in a patient of culture-negative IE. The patient underwent valve replacement surgery and received antibiotics for 5 weeks and survived. Using metagenomic analysis of resected vegetation, we detected Abiotrophia defectiva, which is often associated with culture-negative IE due to its fastidious growth. This method may be useful for pathogen identification in future cases of culture-negative IE.


Pentosidine determination in CSF: a potential biomarker of Alzheimer's disease?
The histopathological hallmarks in Alzheimer's disease (AD) include neuronal cell death, formation of amyloid plaques and neurofibrillary tangles. Glycoxidation plays a crucial role in AD pathogenesis, as pentosidine and Nε- carboxymethyl-lysine (CML), were detected in AD hallmarks, and in vivo cerebrospinal fluid (CSF). However, the definitive role of AGEs in the neuropathology of AD is inconclusive. The aim of this preliminary study was to assess the level of pentosidine in CSF of patients affected by neurological disorders, including probable AD, in order to assess the feasibility of AGEs detection in CSF and to explore pentosidine as a potential biomarker in AD. Twenty-five patients diagnosed with AD (NINCDS ADRDA criteria) and different neurological disorders were enrolled. Diabetic patients were excluded. Pentosidine, CML, amyloid β1-42 were assessed by high performance liquid chromatography (HPLC) by Odetti modified method,and by sandwich ELISA respectively. Our data showed the presence of pentosidine in all CSF samples, a significant increase in CSF pentosidine levels with age (p<0.05) and a significant decreased concentration of pentosidine in four AD subjects (p<0.01), after normalization to CSF protein concentration. The study showed that AGEs concentration in CSF might benefit from age correction, at least for pentosidine, originally addressing a potential systemic age-dependent AGEs accumulation. The significant decrease of CSF pentosidine in AD, even in 4 patients, might conceive that different AGEs inform specific types of neurodegeneration, depending on oxidative stress levels, blood - brain barrier permeability, brain localization and systemic risk factors.


Angiotensin AT1A receptor signal switching in Agouti-related peptide neurons mediates metabolic rate adaptation during obesity.
Resting metabolic rate (RMR) adaptation occurs during obesity and is hypothesized to contribute to failed weight management. Angiotensin II (Ang-II) type 1 (AT1A) receptors in Agouti-related peptide (AgRP) neurons contribute to the integrative control of RMR, and deletion of AT1A from AgRP neurons causes RMR adaptation. Extracellular patch-clamp recordings identify distinct cellular responses of individual AgRP neurons from lean mice to Ang-II: no response, inhibition via AT1A and Gαi, or stimulation via Ang-II type 2 (AT2) receptors and Gαq. Following diet-induced obesity, a subset of Ang-II/AT1A-inhibited AgRP neurons undergo a spontaneous G-protein "signal switch," whereby AT1A stop inhibiting the cell via Gαi and instead begin stimulating the cell via Gαq. DREADD-mediated activation of Gαi, but not Gαq, in AT1A-expressing AgRP cells stimulates RMR in lean and obese mice. Thus, loss of AT1A-Gαi coupling within the AT1A-expressing AgRP neuron subtype represents a molecular mechanism contributing to RMR adaptation.


The inpatient advanced practice nursing roles in a Canadian pediatric oncology unit.
The role of the nurse practitioner has been long established in the outpatient setting in pediatric oncology. The inpatient nurse practitioner role has been described to a lesser extent. This review of the role of the inpatient clinical nurse specialist/nurse practitioner on the 27-bed inpatient oncology unit at the Hospital for Sick Children in Toronto, Ontario, Canada, will describe the role and strategies for its implementation. This role of the clinical nurse specialist/nurse practitioner facilitates the provision of quality care to children and families admitted to the inpatient oncology unit.


Hepatic steatosis in chronic hepatitis B develops due to host metabolic factors: a comparative approach with genotype 1 chronic hepatitis C.
Hepatic steatosis has not been adequately studied in chronic hepatitis B, while it is considered to be a cardinal feature in chronic hepatitis C and to be mainly metabolically induced in patients infected with genotype 1. We investigated the prevalence of and the parameters associated with steatosis in HBeAg-negative chronic hepatitis B. We studied 213 patients with HBeAg-negative chronic hepatitis B and compared them with 163 patients with genotype-1 chronic hepatitis C. Steatosis was semi-quantitatively graded. Steatosis was significantly less frequent in chronic hepatitis B than chronic hepatitis C (60% versus 72%, P=0.016), but there was no difference in the prevalence of moderate/severe steatosis. In chronic hepatitis B, steatosis was associated only with higher body mass index (P=0.002), while moderate/severe steatosis was associated only with higher body mass index (P=0.043) and diabetes (P=0.031). Steatosis was relatively less frequent in chronic hepatitis B than chronic hepatitis C non-diabetic, normal-weight patients (45.6% versus 62.5%, P=0.063), but it did not differ in diabetic and/or overweight/obese patients with chronic hepatitis B or chronic hepatitis C. Hepatic steatosis in HBeAg-negative chronic hepatitis B (a) is less frequent than in genotype-1 chronic hepatitis C, (b) is mainly associated with presence of host metabolic factors, such as high body mass index and diabetes and (c) does not seem to be associated with the severity of liver histological lesions.


High doses of intrapleural cisplatin in a case of malignant pleural mesothelioma. Clinical observations and pharmacokinetic analyses.
The authors report a feasibility study of intrapleural cisplatin in a patient with inoperable malignant pleural mesothelioma. Total and filterable platinum in pleural effusion and in plasma were monitored for two intrapleural courses of 120 mg/m2 cisplatin, and a weekly schedule was adopted. Platinum concentrations in pleural effusion, plasma, and urine were determined by flameless atomic absorption spectroscopy. A lower peak of filterable platinum in plasma, a decrease in systemic filterable platinum exposure (AUC [area under the concentration-time curve]), and a greater pleural exposure to filterable platinum were observed after Course 2 compared with Course 1. After the second cycle of intrapleural treatment, the systemic AUC for filterable platinum was reduced by 40%. The authors' findings may have some implications for the clinical use of intrapleural chemotherapy with high doses of cisplatin. Both infusions of cisplatin were generally well tolerated by the patient and were associated with the local pharmacologic advantage of sustained exposure to cisplatin of the pleural cavity. No sign of myelosuppression, neuropathy, or ototoxicity was observed, and acute toxicity consisted of mild nausea, vomiting, and prolonged anorexia. A transient presence of granular casts was the only observed nephrotoxic effect of cisplatin. Excellent local control of the disease with absence of recurrence of the effusion was observed.


Complications and outcomes after pulmonary resection for cancer in patients 80 to 89 years of age.
Patients 80 years or older often present with potentially resectable cases of non-small cell lung cancer. Whether such patients should undergo surgical treatment is becoming increasingly important in this rapidly aging society. From April 1997 through March 2004, 40 consecutive patients with non-small cell lung cancer who were 80-88 years of age underwent complete resection of their tumors, as confirmed pathologically. We reviewed preoperative data including gender, age, history of smoking, pulmonary function, co-morbidity, and induction/adjuvant therapy. Perioperative data consisted of surgical procedure, operative morbidity and mortality, histopathologic type, pathologic stage, and outcome. The procedures comprised 16 lobectomies (40%), 12 segmentectomies (30%), and 12 wedge resections (30%). The histopathologic diagnosis was adenocarcinoma in 22 patients, squamous cell carcinomas in 11, large cell carcinomas in 4, adenosquamous cell carcinomas in 2, and neuro-endocrine cell carcinoma in 1. The disease stage was IA in 21 patients, IB in 14, IIB in 3, and IIIA in 2. There was no perioperative mortality. Eight patients had non-lethal complications (20%), including five with cardiopulmonary complications (parenchymal air leaks persisting for more than 7 days in two patients, interstitial pneumonia in one, bacterial pneumonia in one, and moderate arrhythmias in one) and three with minor complications (depression or confusion). The actuarial survival rates of the 40 patients, including deaths from all causes, were 92.4, 71.6, and 56.9% at 1, 3, and 5 years, respectively. In patients with stage I disease, the respective survival rates were 94.3, 74.3, and 57.3%. Advanced age is not a contraindication to curative resection in patients 80-89 years of age with stage I non-small cell lung cancer.


Age and the amplitude of accommodation measured using dynamic retinoscopy.
Dynamic retinoscopy (DR) is a procedure for assessing the accommodative response using a standard clinical instrument. The present study compared measurements of the amplitude of accommodation (AA) obtained using this technique with two subjective methods (modified push-down and minus lens). Additionally, the expected ranges for AA when measured by DR were determined. AA was measured in 1298 subjects between 5 and 60 years of age using the three techniques described above. Subjects were grouped into 5-year bins, and a descriptive univariate analysis of the data performed. Goodness-of fit plots were constructed to examine the overall model fit. Centile curves were calculated from the final model. Mean values of AA obtained using DR were significantly lower than for the two subjective techniques. For the DR findings, no significant change was observed between 5 and 19 years of age (mean AA = 8.3 D) and between 45 and 60 years of age (mean AA = 0.6 D). AA values as a function of age were best fit by the polynomial regression equation: logAA = 1.93 + 0.49(age) - 0.19(age)(2) . Measurements of AA determined using DR are significantly lower than the normative subjective findings published previously. This difference is at least partly due to the depth-of-field of the eye. These norms markedly overestimate accommodative responsivity. DR provides a simple technique for quantifying accommodation in the clinical setting.


C-ABI3, the carrot homologue of the Arabidopsis ABI3, is expressed during both zygotic and somatic embryogenesis and functions in the regulation of embryo-specific ABA-inducible genes.
A carrot gene homologous to the ABI3 gene of Arabidopsis was isolated from a carrot somatic embryo cDNA library and designated C-ABI3. The sequence of C-ABI3 was very similar to those of ABI3 of Arabidopsis and VP1 of maize in certain conserved regions. The expression of C-ABI3 was detected specifically in embryogenic cells, somatic embryos and developing seeds. Thus, expression of C-ABI3 was limited to tissues that acquired desiccation tolerance in response to endogenous or exogenous abscisic acid (ABA). Endogenous levels of ABA in seeds increased transiently and then desiccation of seeds started. The expression of C-ABI3 in developing seeds was observed prior to the increase in levels of endogenous ABA that was followed by desiccation of seeds. In transgenic mature leaves in which C-ABI3 was ectopically expressed, expression of ECP31, ECP63 and ECP40 was induced by treatment with ABA, which indicates that the expression of ECP genes was controlled by the pathway(s) that involved C-ABI3 and ABA. This suggests that C-ABI3 has the same function as VP1/ABI3 factor in carrot somatic embryos.


Quality and cost-effectiveness analyses of home-visit nursing based on the frequency of nursing care visits and patients' quality of life: A pilot study.
This pilot study aimed to analyze the cost-effectiveness of visiting nursing care, to establish a new evaluation method considering both the quality and cost of visiting nursing care. Participants were 384 caregivers from 10 certified home-visit nursing agencies that support patients in severe conditions in Japan. They completed a survey assessing the number of nursing care visits carried out in November 2016, visiting nursing receipt data for 1 month of study and quality of life (QOL), as measured by the EuroQol-5 Dimension at their last visit, which took place 1 month later. We categorized participants into low-charge and high-charge groups. In the low-charge group, no relationship was found between high QOL and frequency of implementation of each type of care. In the high-charge group, participants with high frequencies of "medicine management and instruction," "description and guidance for diseases and treatment," and "nutrition and diet care" had higher levels of QOL. This research might contribute to establishing a cost assessment system for home-visit nursing care in Japan, which is expected to be useful in countries where the average age of the population is increasing. Care provided by visiting nurses might be divided into care items that related or did not relate to QOL. Therefore, when evaluating the quality and cost-effectiveness of visiting nursing care, it is necessary to construct an evaluation system that considers these aspects and obtain appropriate data. Geriatr Gerontol Int 2020; 20: 36-41.


Elastic pneumatic tourniquet cuff can reduce postoperative thigh pain after total knee arthroplasty: a prospective randomized trial.
Tourniquet use is associated with complications such as thigh pain, skin problems, and deep vein thrombosis (DVT). This prospective study aimed to evaluate the efficacy and safety of the pneumatic tourniquet system using an elastic cuff and limb occlusion pressure (LOP) in total knee arthroplasty (TKA). The hypothesis of this study was that an elastic cuff tourniquet would result in less postoperative thigh pain after TKA. This prospective randomized controlled trial involved a total of 98 patients who underwent primary TKA. They were randomized into two groups: tourniquet system using an elastic cuff and LOP group (Group E) and tourniquet system using a conventional-cuff and LOP group (Group C). Outcomes including postoperative thigh pain assessed using a visual analog scale (VAS), serum muscle enzymes, recommended tourniquet pressure (RTP), bloodlessness of surgical field, surgical time, incidence of DVT, and the frequency of rescue analgesic use after surgery, were compared between groups. Patients in Group E experienced significantly less thigh pain compared to those in Group C on postoperative day 4 (P = 0.01) and day 7 (P = 0.04). The difference between RTP and systolic blood pressure was significantly lower in Group E (P = 0.045). One case of thigh DVT was found in Group E, while no such cases were found in Group C. One and two cases of poor bloodless surgical fields were observed in Group E and Group C, respectively. There was no significant difference in surgical time, levels of serum muscle enzymes, and the frequency of rescue analgesic use between the two groups. The pneumatic tourniquet system using an elastic cuff and LOP reduced early postoperative thigh pain more effectively than did the tourniquet system using a conventional cuff and LOP. # KCT0003149 . Registered August 17, 2018 - Retrospectively registered.


On the spectacular structural isomorphism between CnHs monoradical and Cn+sHs+3 diradical benzenoid hydrocarbons: from reactive intermediates to vacancy (Hole) defects in graphite.
The formula/structure informatics of monoradical and diradical benzenoid hydrocarbons that are potential reactive intermediates is studied. Some new enumeration and structural results with analytical expressions are presented. The topological paradigm and one-to-one correspondence between the monoradical and diradical constant-isomer series is demonstrated. Constant-isomer benzenoid monoradicals of the formula CnHs have a one-to-one correspondence in isomer number and topology to constant-isomer diradicals of the formula Cn+sHs+3. Some electronic properties of benzenoid radicals are delineated. Excising out a monoradical or diradical benzenoid carbon molecule from a perfect hexagonal graphite layer leaves a matching monoradical or diradical vacancy hole defect called an antimolecule; this observation can be generalized to include excising out all nondisjoint and obvious benzenoid polyradicals from a perfect (Kekuléan) hexagonal graphite layer. It is shown that the characteristics of graphite vacancies (antimolecules) can be deduced from knowledge about the carbon molecules removed in their formation.


Factors regulating the induction of ornithine decarboxylase in fetal rat liver cells in culture.
Various hormonal and non-hormonal agents were tested for their ability to induce ornithine decarboxylase (EC 18.104.22.168) in primary cultures of fetal rat liver cells that retain many of the differentiated functions of hepatocytes. The only agents to induce ornithine decarboxylase in this cell type were fetal calf serum, prostaglandin E1 and cyclic AMP derivatives. Also, the amino acid arginine would induce ornithine decarboxylase in this cell type following arginine starvation for 24 h. These observations are in contrast to the wide range of hormones, e.g. insulin, hydrocortisone, glucagon and growth hormone, than can induce ornithine decarboxylase in vivo in the adult rat liver but which are all without effect on fetal rat liver cells.


[Methods of treatment of perferating plantar pain by using a pneumatic sole].
A--A natural hydrostatic phenomenon, at the level of the ends of the plantar arcs, diffuses body weight, as PAIN plays the role of outsentry (fig.--1) (5); B--Plantar perforating ulceration (PPU) is caused by a combination of INSENSITIVITY and TRAUMATIS (1); C--The patient reposing, as body weight (traumatism) effects disappear, cicatrization process can be easily observed; D--PNEUMATIC INSOLE, being elastic, diffuses localized compression at the ends of the plantar arcs, reduces attrition, makes easier blood circulation, as well as cure and prophylaxis of PPU (fig.--6) (3).


Promotion Strategies of Hole Transport Materials by Electronic and Steric Controls for n-i-p Perovskite Solar Cells.
Hole transport materials (HTMs) play a requisite role in n-i-p perovskite solar cells (PSCs). The properties of HTMs, such as hole extraction efficiency, chemical compatibility, film morphology, ion migration barrier, and so on, significantly affect PSCs' power conversion efficiencies (PCEs) and stabilities. Up till now, researchers have devoted much attention to developing new types of HTMs as well as promoting pristine HTMs using numerous strategies. In this Review, we summarize the design strategies of various common HTMs for n-i-p PSCs are comprehensively discussed from two separate aspects (additive and non-additive engineering). Additive engineering generally tunes electronic properties of HTMs while non-additive engineering basically modifies their steric structures. Critical analysis and comparison between these design strategies are provided, considering the overall PCEs and stabilities of PSCs. Finally, a brief perspective on future promising design strategies for HTMs is given, in order to fabricate efficient and stable n-i-p devices for the commercialization of PSCs.


Forearm vasoconstrictor response to ouabain: studies in patients with mild and moderate essential hypertension.
The dependence of arteriolar vasoconstrictor tone on the activity of Na+,K+-ATPase was studied in 17 normotensive subjects (NT) and 28 patients with essential hypertension (EH) by measuring the response in forearm blood flow and vascular resistance to intraarterial infusion of the Na+,K+-ATPase inhibitor ouabain. Basal plasma aldosterone concentrations were elevated in mild (n = 14) and moderate (n = 14) EH patients as compared with NT (p less than 0.001 for both) and correlated positively with intraarterial diastolic blood pressure (r = 0.551, p less than 0.001). Ouabain in incremental doses of 0.4-16 micrograms/100 ml tissue induced a vasoconstrictor response in the forearm with a maximal effect to 8 micrograms/100 ml tissue, which was not associated with an increase in regional noradrenaline release. The vasoconstrictor response to ouabain, 8 micrograms/100 ml, expressed as the percentage change in the ratio of forearm vascular resistance (FR) on the experimental side versus the control side, was 29.6 +/- 6.8% in NT (p less than 0.001); 51.9 +/- 8.4% in mild EH (p less than 0.001), and 36.0 +/- 12.7% in moderate EH (p less than 0.05). The vasoconstrictor response was greater (p less than 0.05) in patients with mild EH than in NT but did not differ in NT and patients with moderate EH. Vascular reactivity in the forearm, as assessed by intraarterial infusions of noradrenaline (3, 8, and 20 ng/min/100 ml tissue), did not differ in NT (n = 9) and patients with mild (n = 9) or moderate (n = 9) EH. The results suggest increased activity of arteriolar Na+,K+-ATPase in mild EH, which may represent a mechanism counteracting an accumulation of intracellular sodium and thereby an early increase in forearm vascular resistance (FR).(ABSTRACT TRUNCATED AT 250 WORDS)


Concanavalin A-mediated agglutination of 3T3 cells after exposure to UV-irradiated herpes simplex virus.
Studies were made to determine the effect of UV-irradiation of herpes simplex virus (HSV) on Concanavalin A (Con-A)-mediated agglutination of 3T3 cells. There were three different phases of agglutination by Con-A of cells infected with HSV. The agglutinability began to increase from 3 or 4 hr, or 72 hr after exposure of cells to HSV. The early-appearing agglutinability was further divided into two phases, based on its sensitivity to metabolic inhibitors. These were tentatively called "Early 1 or inhibitor sensitive", "Early 2 or inhibitor insensitive" and "Late" agglutinability. "Early 1" agglutination, detected from 3 hr post infection (pi), was induced by treating cells with HSV, either active or UV-irradiated for less than 5 min and was inhibited when actinomycin D (1 microgram/ml) or cycloheximide (50 microgram/ml) was added to the cultures. "Early 2" agglutination began to increase from 4 hr pi when cells were inoculated with HSV irradiated for 7 to 20 min and was not affected by either inhibitor. HSV irradiated for 6 min failed to induce either agglutinability. "Late" agglutination, observed 72 hr pi, was detected in cultures which had been treated with HSV irradiated for 4 to 15 min. Among those, virus irradiated for 6 to 8 min was most efficient. HSV-transformed cells were also agglutinated without exception by low concentrations of Con-A.


Retinal venous pressure in chronic smokers.
The overall aim of this study was to determine retinal venous pressure (RVP) in healthy chronic smokers and compare values to those of healthy non-smokers. Both eyes of 25 healthy chronic smokers and 41 healthy non-smokers were included. Measurements of RVP were performed by means of contact lens ophthalmodynamometry. Ophthalmodynamometry is done by applying increasing force on the eye via a contact lens. If a spontaneous venous pulsation was present, it was noted. If not, the compressive force was increased until the first venous pulsation was detected, and the measurement value was fixed and read. RVP was calculated as the sum of pressure increase induced by the instrument and intraocular pressure. Smokers had a significantly higher frequency of spontaneous venous pulsations than non-smokers (p < 0.001). Mean values of RVP were slightly lower in smokers than in non-smokers: 15.3 and 15.5 (smokers) versus 15.9 and 16.2 (non-smokers) for the right and left eye, respectively; however, the difference in RVP between the two groups did not reach significance. There was no significant difference in blood pressure between the two groups, but heart rate was significantly higher in smokers (p = 0.043). RVP values may differ in healthy smokers than in non-smokers. Therefore, smoking habits should be considered when interpreting RVP results.