Antibiotic properties of Satureja montana L. hydrolate in bacteria and fungus of clinical interest and its impact in non-target environmental microorganisms.
The aim of this study was to analyse the microbicidal and microbiostatic activity of S. montana hydrolate L., the water-soluble fraction of the hydro-distillation process used to obtain the essential oil, on 14 Gram-positive and Gram-negative bacteria and a fungus of clinical interest. To consider whether this hydrolate is a more environmentally friendly alternative to traditional antibiotics, its effect on non-target microorganisms in the aquatic and terrestrial environment was analysed using natural soil and river microorganism communities, characterized through 16S rRNA gene sequencing. Results showed that S. montana hydrolate was especially effective (25% v/v concentration) against Pasteurella aerogenes, Streptococcus agalactiae and Acinetobacter baumannii (priority 1, WHO). It was also a microbicide for a further 7 bacterial strains and the fungus Candida albicans (50% v/v concentration). The river and soil communities exposed to the hydrolate showed a decrease in their growth, as well as a decrease in their ability to metabolize polymers and carbohydrates (soil microorganisms) and polymers, carboxylic and ketone acids (river microorganisms). Hydrolates could be an alternative to conventional antibiotics, but their impact on the environment must be taken into account.


Practice advisory: Etanercept for poststroke disability: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology.
To review evidence regarding the effectiveness, safety, and tolerability of etanercept used to treat patients with poststroke disability. We searched MEDLINE and the Cochrane Central Register of Controlled Trials for studies of adult patients with poststroke disability treated with etanercept in order to improve their functional status. We rated each study for risk of bias (Class I-IV) using the American Academy of Neurology therapeutic classification of evidence scheme. Practice recommendations were formulated on the basis of the strength of the evidence and assessments of potential benefits, potential harms, and patient preferences. Two case series were identified, and both reported clinical improvements 3 weeks following treatment across a wide range of functional domains. However, both studies were rated Class IV because of poor methodologic quality (i.e., high risk of bias). For patients with poststroke disability, the evidence is insufficient to support or refute a benefit of etanercept for the treatment of poststroke disability. Clinicians should counsel patients considering etanercept for treatment of poststroke disability that the evidence is insufficient to determine the treatment's effectiveness and that it may be associated with adverse outcomes and high cost (Level U).


Pilot Randomized Controlled Trial of an Advance Care Planning Video Decision Tool for Patients With Advanced Liver Disease.
Transplant-ineligible patients with advanced liver disease rarely receive timely advance care planning (ACP). Tools are needed to educate these patients about medical interventions available at the end of life to promote ACP. This single-site pilot randomized controlled trial assessed the feasibility, acceptability, and preliminary efficacy of an ACP video decision support tool for improving transplant-ineligible advanced liver disease patients' knowledge about and preferences for end-of-life care. Intervention participants watched a 5-minute video depicting 3 levels of goals of care: life-prolonging care (cardiopulmonary resuscitation [CPR] and intubation), life-limiting care (hospitalization, no CPR/intubation), and comfort care. Control subjects received only a verbal narrative of these 3 levels of goals of care. The primary outcome was feasibility (≥60% enrollment rate). Secondary outcomes included acceptability of the video, patients' knowledge of end-of-life care options (6-item test; range, 0-6), and postintervention goals-of-care and CPR or intubation preferences. We enrolled 85% (n = 50 of 59) of eligible patients randomized to the video (n = 26) or verbal (n = 24) arm. In the video arm, 81% of patients reported being very comfortable watching the video. Patients in the video arm had higher mean knowledge scores (5.7 vs 4.8; P < .001) and were less likely to prefer to receive CPR compared with patients in the verbal arm (35% vs 63%; P = .09). An ACP video decision support tool to improve knowledge about and preferences for end-of-life care is both feasible and highly acceptable to transplant-ineligible patients with advanced liver disease with a high enrollment rate and promising preliminary efficacy. Future studies should examine the efficacy of the ACP video for enhancing the quality of their end-of-life care. (ClinicalTrials.gov, Number: NCT03557086).


Pre- and perinatal complications and risk for bipolar disorder: a retrospective study.
Many studies have reported that obstetric complications are risk factors for schizophrenia, but few studies have examined whether complications increase risk for bipolar disorder. Bipolar-disorder probands and their adult siblings were diagnosed using DSM-III-R criteria. Obstetrical data from maternal reports were scored, blind to diagnosis, applying published scales that take into account number and severity of complications. Obstetric complication scores were significantly worse in probands than siblings without mood disorders. Probands had relatively severe symptoms; research using more heterogeneous samples is needed. Results suggest obstetric complications are etiologically significant in bipolar disorder.


Natural Dietary Supplement, Carvacrol, Alleviates LPS-Induced Oxidative Stress, Neurodegeneration, and Depressive-Like Behaviors via the Nrf2/HO-1 Pathway [Retraction].
[This retracts the article DOI: 10.2147/JIR.S294413.].


Patterns and Predictors of Health Care Utilization After Pediatric Concussion: A Retrospective Cohort Study.
To characterize types, duration, and intensity of health care utilization following pediatric concussion and to identify risk factors for increased post-concussion utilization. A retrospective cohort study of children 5 to 17 years old diagnosed with acute concussion at a quaternary center pediatric emergency department or network of associated primary care clinics. Index concussion visits were identified using International Classification of Diseases, Tenth Revision, Clinical Modification codes. We analyzed patterns of health care visits 6 months before and after the index visit using interrupted time-series analyses. The primary outcome was prolonged concussion-related utilization, defined as having ≥1 follow-up visits with a concussion diagnosis more than 28 days after the index visit. We used logistic regressions to identify predictors of prolonged concussion-related utilization. Eight hundred nineteen index visits (median [interquartile range] age, 14 [11-16] years; 395 [48.2%] female) were included. There was a spike in utilization during the first 28 days after the index visit compared to the pre-injury period. Premorbid headache/migraine disorder (adjusted odds ratio (aOR) 2.05, 95% confidence interval [CI] 1.09-3.89) and top quartile pre-injury utilization (aOR 1.90, 95% CI 1.02-3.52) predicted prolonged concussion-related utilization. Premorbid depression/anxiety (aOR 1.55, 95% CI 1.31-1.83) and top quartile pre-injury utilization (aOR 2.29, 95% CI 1.95-2.69) predicted increased utilization intensity. Health care utilization is increased during the first 28 days after pediatric concussion. Children with premorbid headache/migraine disorders, premorbid depression/anxiety, and high baseline utilization are more likely to have increased post-injury health care utilization. This study will inform patient-centered treatment but may be limited by incomplete capture of post-injury utilization and generalizability.


Neovascularization in diabetes and its complications. Unraveling the angiogenic paradox.
Diabetes mellitus (DM) is a chronic metabolic disease characterized by the presence of hyperglycemia, which can lead to many complications over time. These complications, such as nephropathy, retinopathy, neuropathy, impaired wound healing and accelerated atherosclerosis, are implicated with a large number of cellular and subcellular changes on vessels. In agreement, evidence indicates that in retinopathy, nephropathy and atherosclerotic plaque, there is excessive angiogenesis, whereas in wound healing and myocardial perfusion, blood vessel growth is impaired. Despite the awareness of this angiogenic paradox, many questions remain unanswered. This review aims at highlighting the different microvascular and macrovascular complications that are often concurrent in diabetic patients. A revision of the recent findings published in the literature regarding the angiogenic paradox will be performed. Apparently, endothelial dysfunction, as well as molecules such as vascular endothelial growth factor (VEGF) and hypoxia-inducible factor (HIF) play a major role in diabetic vascular complications. Specific tissues with impaired angiogenesis exhibit microenvironment features, such as increased PAI-1/uPA ratio and decreased blood flow, whereas TGFbeta increases extracellular matrix deposition, preventing the vascularization process. In addition, the monocytes/macrophages are important in endothelium activation for arteriogenesis and its arteriogenic response is reduced, leading to impaired collateral artery growth. Moreover, molecular mechanisms involved will be addressed, including abnormalities in growth factor, cytokines and metabolic derangements.


What constitutes evidence in hospital new drug decision making?
In National Health Service hospitals in the UK the introduction of new drugs is controlled by a local Drug and Therapeutics Committee (DTC), which is expected to apply the principles of evidence-based medicine (EBM). In the light of growing expenditure on drugs, there is interest in how the decisions are made that lead to the local acceptance or rejection of a new drug. In this study the DTCs of two general hospitals were observed, tape-recorded and analysed to determine what was considered as evidence and how it was used in decision making. Evidence, as constituted by DTC members, was issues that affected the decision-making process and included: clinical trial data, cost, pre-existing prescribing of the drug, pharmaceutical company activities, decisions of other DTCs, patient demand, clinician excitement, and personality of the applicant. Debate usually started with a discussion of the scientific evidence, then the cost would be considered. Often this evidence was either inadequate or insufficient enough for a locally implementable decision and further types of evidence would be brought in to try and estimate the likely impact of adopting the new drug. EBM, while used in decision making, was supplemented by local knowledge, although decisions were accounted for in the language of scientific rationality. Both abstract scientific rationality and the local rationality of practical healthcare provision were present in the decisions of the DTCs on the adoption, or otherwise, of new drugs into local formularies and healthcare. We suggest the coming together of local and abstract in local decision-making needs to be taken into account when formulating policy and providing decision support.


Associations between poor gross and fine motor skills in pre-school and peer victimization concurrently and longitudinally with follow-up in school age - results from a population-based study.
Children with poor motor skills are at increased risk of peer victimization. However, it is unclear whether poor gross and fine motor skills are differently linked to peer victimization among pre-school and schoolchildren. To investigate associations between poor gross and fine motor skills measured in pre-school and the associations to peer victimization measured concurrently and in school age. Data from the Norwegian Mother, Father and Child Cohort Study (MoBa), and the Medical Birth Registry of Norway were used. Participants with complete questionnaires at 3, 5, and 8 years (n = 23 215) were included. A longitudinal design and an autoregressive cross-lagged model were used to investigate if poor gross and fine motor skills at 3 and 5 years predicted peer victimization at 5 and 8 years. Because emotional difficulties are associated with both motor skills and peer victimization, the results were adjusted for emotional difficulties. Only poor fine motor skills at 3 years had a significant association to peer victimization at 5 years. Poor gross motor skills at 5 years had a stronger association to peer victimization measured concurrently compared to poor fine motor skills, and only poor fine motor skills at 5 years was significantly linked to peer victimization at 8 years. No gender difference was found between these paths. Teachers and parents should be aware that motor skills predict peer victimization, and that poor gross and fine motor skills have different associations to peer victimization measured at different ages.


RGF1-RGI1, a Peptide-Receptor Complex, Regulates Arabidopsis Root Meristem Development via a MAPK Signaling Cascade.
Root growth is maintained by the continuous division of cells in the apical meristem. ROOT MERISTEM GROWTH FACTOR 1 (RGF1) is a critical peptide hormone regulating root stem cell niche maintenance. Previous studies discovered that five closely related leucine-rich repeat receptor-like protein kinases (LRR-RLKs), named RGF1 INSENSITIVES (RGIs) or RGF1 RECEPTORS (RGFRs), are able to perceive the RGF1 signal and redundantly control root stem cell niche maintenance. RGF1 regulates root meristem activity mainly via two downstream transcription factors, PLETHORA 1 (PLT1) and PLT2. Regulatory proteins connecting cell surface RGF1-RGI1 and nuclear PLTs, however, were not identified. Here, we report that the mitogen-activated protein (MAP) kinase kinase 4 (MKK4) and MAP kinase 3 (MPK3) were co-immunoprecipitated with RGI1-FLAG after Arabidopsis seedlings were treated with RGF1. Genetic and biochemical assays confirmed that MKK4 and MKK5, and their downstream targets MPK3 and MPK6, are essential RGI-dependent regulators of root meristem development. In addition, we found that the MKK4/MKK5-MPK3/MPK6 module functions downstream of YDA, a MAPKKK. Our results demonstrate that RGF1-RGI1 regulate the expression of PLT1/PLT2 via a YDA-MKK4/MKK5-MPK3/MPK6 signaling cascade.


More than words! A narrative review of the use of the projective technique of word association in the studies of food consumer behavior: Methodological and theoretical implications.
Word association (WA) is a projective and powerful technique that consists of the spontaneous generation of words from specific stimuli. This technique is used in sociology and psychology studies; however, in the Consumer and Food Science area has gained importance since it allows to explore beliefs, expectations, or attitudes in the context of food consumption behavior. The aim of this work is to present a current status on the use of this technique in the studies of food consumption behavior. A narrative review of the literature was carried out with articles published in four databases: ScienceDirect, Wiley Online Library, Emerald Insight, and Taylor & Francis. Seventy-four articles that show the use of the WA technique in different cultures were selected. WA technique has been applied in different countries, however, it has been primarily used in Latin America. WA has been applied mainly to decipher consumers' perceptions towards different aspects of food, although some works show that WA serves to understand beliefs, expectations, impressions, attitudes, and even to conceptualize different categories of food from the language of consumers. Some theoretical and methodological implications are discussed regarding the use and application of this projective technique.


Molecular defects identified by whole exome sequencing in a child with Fanconi anemia.
Fanconi anemia is a rare genetic disease characterized by bone marrow failure, multiple congenital malformations, and an increased susceptibility to malignancy. At least 15 genes have been identified that are involved in the pathogenesis of Fanconi anemia. However, it is still a challenge to assign the complementation group and to characterize the molecular defects in patients with Fanconi anemia. In the current study, whole exome sequencing was used to identify the affected gene(s) in a boy with Fanconi anemia. A recurring, non-synonymous mutation was found (c.3971C>T, p.P1324L) as well as a novel frameshift mutation (c.989_995del, p.H330LfsX2) in FANCA gene. Our results indicate that whole exome sequencing may be useful in clinical settings for rapid identification of disease-causing mutations in rare genetic disorders such as Fanconi anemia.


Initiating antiepileptic drug treatment and characteristics of drugs.
This chapter covers the main steps involved in the initiation of antiepileptic drug therapy. Aspects covered specifically include the decision whether or not to initiate treatment, the selection process of a drug of first choice for a given patient with a particular seizure type or epilepsy syndrome, and the process of initiating therapy with the selected drug of first choice. Suggested choices of antiepileptic drugs by seizure type or epilepsy syndrome are summarized in a table. In an appendix, these drugs are reviewed individually with regard to their clinical use. The emphasis is on initial dose, dosage escalation, common and serious adverse effects, baseline evaluation, monitoring of therapy, and relevant drug interactions.


Effects of metal chelating agents on the oxidation of lipids induced by copper and iron.
The non-enzymatic oxidations of soybean phosphatidylcholine liposomes, methyl linoleate micelles and low-density lipoprotein in aqueous dispersions induced by copper and iron have been studied aiming specifically at elucidating the action of the metal chelating agents such as ethylenediaminetetraacetic acid disodium salt (EDTA), nitrilotriacetic acid (NTA), adenosine-5'-diphosphate disodium salt (ADP), desferrioxamine (DFO), penicillamine (PCM), and triethylene tetramine (TTM). The effects of chelators on chemiluminescence emitted from its probe luminol in the decomposition of tert-butyl hydroperoxide by metal ion were also studied. The effects of chelators on the oxidations depended both on the metal ion and the substrate. Namely, in the oxidations of both liposomes and micelles, EDTA and NTA suppressed the copper-induced oxidations, whereas they enhanced the oxidations induced by iron. ADP had little effect, while PCM and TTM had accelerating effect for both metal ions. On the other hand, in the oxidation of LDL, none of these chelators enhanced the oxidation. Especially, TTM and PCM suppressed the copper-induced oxidation of LDL, suggesting that the chelating agents blocked the access of the metal ion to the hydroperoxide within LDL. The effects of chelators on chemiluminescence emission were similar to those on the oxidations of liposomes and micelles. The cyclic voltammograms of metal complexes were also measured. The multiple effects of chelators on the rate of non-enzymatic, metal-catalyzed oxidations of lipids were interpreted by their influence on redox-potential and accessibility to hydroperoxide of the metal-chelator complex.


"4S" polycyclic aromatic hydrocarbon binding protein. Its role as a benzo(a) pyrene cytosolic carrier to the microsomes of DBA/2N mouse liver.
Rodent liver cytosol and other biological systems contain two proteins that bind polycyclic aromatic hydrocarbons (PAH) in a non covalent manner and that sediment at a different rate when centrifuged on sucrose gradient. The role of the smaller protein ("4S" PAH-BP) was studied. When DBA/2N mouse liver homogenate was incubated with 3H-BaP, most of the radioactivity was found in the microsomal subcellular fraction. The cytosol binding activity apparently decreased but reincubation of the cytosol with the radioactive ligand completely restored "4S" PAH-BP activity. The microsomal uptake of 3H-BaP can be studied in a reconstituted system in which microsomes are incubated with radioactive benzo(a)pyrene in the presence of crude cytosol. In these conditions the microsomal uptake rate of 3H-BaP increased with the temperature and at 37 degrees C ten minutes were required to reach the plateau. When cytosol was substituted by HEDG buffer, the amount of radioactivity found in the microsomes decreased drastically. 0.2 microM was the benzo(a)pyrene concentration required to saturate the microsomes. When microsomes were incubated with ammonium sulfate cytosolic fractions or with homogeneously purified "4S" PAH-BP, the 3H-BaP uptake was restored and reached the maximum with 3 micrograms/ml of purified protein. The radioactive benzo(a)pyrene bound to microsomes was oxidated in the presence of NADPH regenerating system. The oxidated products were discharged from microsomes only when "4S" PAH-BP was either present during the incubation or added at its end. Thus, this protein is able to transfer benzo(a)pyrene to the microsomal metabolization sites and to facilitate the release of oxidized products and, presumably, bind them.


Guided Implant Surgery: A Technique Whose Time Has Come.
Guides used in dental implant surgery add accuracy and an overall predictability. Successful guided implant workflow depends on 3-dimensional image acquisition and precise medical model fabrication. The contemporary process blends acquired images to existing dentition to create implant-specific precise guides. We discuss the overall process, types of guides, and complications to expect during surgery.


Phosphorylation of histone H2AX at M phase in human cells without DNA damage response.
A variant of histone H2A, H2AX, is phosphorylated on Ser139 in response to DNA double-strand breaks (DSBs), and clusters of the phosphorylated form of H2AX (gamma-H2AX) in nuclei of DSB-induced cells show foci at breakage sites. Here, we show phosphorylation of H2AX in a cell cycle-dependent manner without any detectable DNA damage response. Western blot and immunocytochemical analyses with the anti-gamma-H2AX antibody revealed that H2AX is phosphorylated at M phase in HeLa cells. In ataxia-telangiectasia cells lacking ATM kinase activity, gamma-H2AX was scarcely detectable in the mitotic chromosomes, suggesting involvement of ATM in M-phase phosphorylation of H2AX. Single-cell gel electrophoresis assay and Western blot analysis with the anti-phospho-p53 (Ser15) antibody indicated that H2AX in human M-phase cells is phosphorylated independently of DSB and DNA damage signaling. Even in the absence of DNA damage, phosphorylation of H2AX in normal cell cycle progression may contribute to maintenance of genomic integrity.


Synthesis and antithrombotic activity of carbolinecarboxyl RGD sequence.
3S-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid, RGDS, RGDV, RGDF and their linkers were synthesized. The anti-aggregation and adhesion of platelet indicated that the in vitro activities of the linkers remained at the same level as RGDS, RGDV, and RGDF (p>0.05). The antithrombotic activities in vivo suggested, however, that the potencies of RGDS, RGDV and RGDF were enhanced by the introduction of 3S-1,2,3,4-tetrahydro-beta-carboline-3-carboxyl group into their alpha amino group (p<0.05, 0.01 or 0.001).


Isolated adipocytes from growth hormone-treated obese (ob/ob) mice exhibit insulin resistance.
The genetically obese (ob/ob) mouse is a useful model for the study of the diabetogenic action of growth hormone (GH), because treatment of these animals with GH results in decreased responsiveness of their adipose tissue to insulin in vitro. Studies of the mechanisms involved in GH-induced insulin resistance using isolated adipocytes of ob/ob mice have not been possible, however, because of their extreme fragility and the lack of an adequate system for the maintenance of these cells. This study describes a new method for the isolation of ob/ob mouse adipocytes. The isolated cells are stable, viable and metabolically responsive to insulin. In addition, these adipocytes have been maintained in primary culture, in serum-free medium, for up to 3 days. During culture, the cells exhibit large increases in 125I-hGH binding (10-20-fold) and porcine 125I-insulin binding (5-10-fold). The induction of insulin resistance by GH has also been demonstrated in these freshly isolated ob/ob mouse adipocytes. The studies to date indicate that the ob/ob mouse adipocyte system should provide a useful model for detailed studies of the cellular and molecular mechanisms of GH induced insulin resistance.


Associations of Sarcopenia, Handgrip Strength and Calf Circumference with Cognitive Impairment among Chinese Older Adults.
To evaluate the associations of sarcopenia, handgrip strength and calf circumference with cognitive impairment among Chinese older adults. Totally 2,525 older adults were recruited from the Healthy Aging and Biomarkers Cohort Study. Cognitive impairment was assessed by the Chinese Mini-Mental State Examination. Handgrip strength was calculated from the means of the right and left hand values. Calf circumference was measured at the site of maximum circumference of the non-dominant leg. The formula developed by Ishii was used to define sarcopenia. Multiple logistic regression was performed to evaluate the associations of sarcopenia, handgrip strength, and calf circumference with cognitive impairment. The prevalence of cognitive impairment was 34.36%. The adjusted odds ratio ( OR) for cognitive impairment in individuals with sarcopenia was 2.55 [95% confidence interval (95% CI): 1.86-3.50]. Compared with individuals in the first quartile (Q 1) of calf circumference, the adjusted ORs in the second, third, and fourth quartiles (Q 2, Q 3, and Q 4) were 0.75 (95% CI: 0.58-0.96), 0.59 (95% CI: 0.44-0.79), and 0.62 (95% CI: 0.45-0.8), respectively. Compared with individuals in Q 1 of handgrip strength, the adjusted ORs for Q 2, Q 3, and Q 4 were 0.49 (95% CI: 0.38-0.62), 0.31 (95% CI: 0.23-0.41), and 0.30 (95% CI: 0.21-0.44), respectively. Sarcopenia, identified by low handgrip strength and low calf circumference, was positively associated with cognitive impairment.


Comprehensive two-dimensional gas chromatography with a multi-capillary second dimension: a new column-set format for simultaneous optimum linear velocity operation.
Comprehensive two-dimensional gas chromatography (GC×GC) suffers from the impossibility to operate both dimensions at their optimum carrier gas velocity at the same time due to the different inner diameters of the columns typically employed. The use of multiple parallel capillary columns in the second dimension (GC×multi-GC) is studied as a means to achieve simultaneous optimum-velocity operation. A programme written in Microsoft Excel(®) was developed to calculate the efficiency of the two dimensions in GC×multi-GC for different numbers of columns in the second dimension. With the aid of this programme the appropriate number of columns was selected. Columns with maximum repeatability were specifically manufactured to grand suitable performance, i.e. to avoid band broadening effects caused by inter-column variations. 1D-GC experiments were carried out on the columns separately and combined in parallel. The performance of the parallel column set was consistent with that of the individual columns, with over 9100 plates generated (approximately 10,000 plates/m). A GC×multi-GC set-up was successfully installed. Model experiments proved the possibility to operate both dimensions at their optimum linear velocity simultaneously. The suitability of the novel second dimension column format to perform multidimensional separations was also shown for a number of selected applications.


Cat and monkey cortical columnar patterns modeled by bandpass-filtered 2D white noise.
A simple algorithm based on bandpass-filtering of white noise images provides good quality computer reconstruction of the cat and monkey ocular dominance and orientation column patterns. A small number of parameters control the frequency, orientation, "branchedness", and "regularity" of the column patterns. An oriented (anisotropic) bandpass filter followed by a threshold operation models the macaque ocular dominance column pattern and cat orientation column system. An unoriented (isotropic) bandpass filter models the cat ocular dominance column pattern and the macaque orientation column system. The resemblance of computer graphic simulations produced by this algorithm and histological pattern data, is strong. Since this algorithm is very fast, we have been able to extensively explore its parameters space in order to determine filter parameters which closely match the structure of the various cortical systems. In particular, we have applied spectral analysis to our recent computer reconstruction of the macaque ocular dominance column system, and the model produced by the present algorithm is in close agreement with this detailed data analysis.


[Surgical treatment of decubitus ulcers in the area of the ischium, sacrum and trochanter major].
The operative management of pressure sores in the ischial, sacral and trochanteric region is based on the gluteus maximus muscle and its vascularization. Pressure sores in the sacral region were closed with eleven V-Y musculocutaneous flaps, for the ischial region with fifteen pendulum flaps, and for the trochanteric region with eight medial thigh flaps. In the four years follow-up of 24 patients three recurrences occurred and the post-operative morbidity was acceptable. The operative technique and the complications are further discussed.


Regulation of the tumor marker Fascin by the viral oncoprotein Tax of human T-cell leukemia virus type 1 (HTLV-1) depends on promoter activation and on a promoter-independent mechanism.
Adult T-cell leukemia/lymphoma is a highly infiltrative neoplasia of CD4(+) T-lymphocytes that occurs in about 5% of carriers infected with the deltaretrovirus human T-cell leukemia virus type 1 (HTLV-1). The viral oncoprotein Tax perturbs cellular signaling pathways leading to upregulation of host cell factors, amongst them the actin-bundling protein Fascin, an invasion marker of several types of cancer. However, transcriptional regulation of Fascin by Tax is poorly understood. In this study, we identified a triple mode of transcriptional induction of Fascin by Tax, which requires (1) NF-κB-dependent promoter activation, (2) a Tax-responsive region in the Fascin promoter, and (3) a promoter-independent mechanism sensitive to the Src family kinase inhibitor PP2. Thus, Tax regulates Fascin by a multitude of signals. Beyond, using Tax-expressing and virus-transformed lymphocytes as a model system, our study is the first to identify the invasion marker Fascin as a novel target of PP2, an inhibitor of metastasis.


Synthesis, conformational analysis and glycosidase inhibition of bicyclic nojirimycin C-glycosides based on an octahydrofuro[3,2-b]pyridine motif.
A set of bicyclic iminosugar C-glycosides, based on an octahydrofuro[3,2-b]pyridine motif, has been synthesized from a C-allyl iminosugar exploiting a debenzylative iodocycloetherification and an iodine nucleophilic displacement as the key steps. The halogen allowed the introduction of a range of aglycon moieties of different sizes bearing several functionalities such as alcohol, amine, amide and triazole. In these carbohydrate mimics the fused THF ring forces the piperidine to adopt a flattened 4C1 conformation according to NMR and DFT calculations studies. In their deprotected form, these bicycles were assayed on a panel of 23 glycosidases. The iminosugars displaying hydrophobic aglycon moieties proved to be superior glycosidase inhibitors, leading to a low micromolar inhibition of human lysosome β-glucosidase (compound 11; IC50 = 2.7 μM) and rice α-glucosidase (compound 10; IC50 = 7.7 μM). Finally, the loose structural analogy of these derivatives with Thiamet G, a potent OGA bicyclic inhibitor, was illustrated by the weak OGA inhibitory activity (Ki = 140 μM) of iminosugar 5.


Plasma osteoprotegerin level is associated with hemorrhagic transformation in stroke patients who underwent endovascular thrombectomy.
Osteoprotegerin (OPG) is a component of the tumor necrosis factor receptor superfamily. Several studies have shown a relationship between OPG and cardiovascular disease. We investigated the association between plasma OPG levels and hemorrhagic transformation in stroke patients who received endovascular thrombectomy (EVT). We prospectively enrolled 360 patients diagnosed with acute ischemic stroke and performed EVT from April 2014 to December 2020. Blood sampling for plasma OPG was performed after fasting for 12 h after EVT. Hemorrhagic transformation was defined using the definition and classification of the European Cooperative Acute Stroke Study-3 trial. Of all the included patients, 130 (36.1%) experienced hemorrhagic transformation. The mean ± standard deviation of the plasma OPG concentrations was 200.2 ± 74.4 pg/mL. In multivariable analysis, after adjusting for age, sex, body mass index (BMI), and variables with p < 0.1 in univariable analysis (diabetes mellitus, atrial fibrillation, coronary artery disease, alcohol intake, current smoking, NIHSS, ASPECT score, mass effect, hemoglobin, vitamin D 25(OH)D), increased plasma OPG concentration was independently related to any hemorrhagic transformation (highest tertile vs. lowest tertile of OPG; odds ratio [OR] 2.31, 95% confidence interval [CI] (1.29-4.14), p = 0.005) and severity of hemorrhagic transformation (OR 2.92, 95% CI (1.66-5.12), p = 0.001). Our results demonstrate that increased plasma OPG level is related to the occurrence and severity of hemorrhagic transformation in patients with cerebral infarction who receive EVT.


Comprehensive pharmacokinetics of urinary human follicle stimulating hormone in healthy female volunteers.
The study determined the pharmacokinetics of urinary human follicle stimulating hormone (u-hFSH) in 12 down-regulated healthy female volunteers. Following pituitary desensitization, baseline FSH serum levels were measured over a 24-hour period. Then each subject received, in random order, single doses of u-hFSH (Metrodin), 75 IU, 150 IU and 300 IU iv, and 150 IU im on four occasions separated by washout periods of one week. Blood and urine samples were collected at preset times. FSH levels were measured by a immuno-radiometric assay and an in vitro rat granulosa cells aromatase bioassay. All doses of u-hFSH were well tolerated. After an iv bolus, the pharmacokinetics of FSH were well described by a two-compartment open model. Immunoassay data showed that the total exposure to FSH was proportional to the administered dose. Mean total clearance of FSH was approximately 0.5 L.h-1 and renal clearance was 0.14 L.h-1. The volume of distribution at steady-state was around 8 liters. The distribution half-life was 2 h and the terminal half-life nearly one day. After im injection, almost two thirds of the administered dose was available systemically. The in vitro bioassay confirmed this pharmacokinetic analysis. The estimation of the elimination half-life of around one day indicates that the maximal effect of a given dose of u-hFSH administered daily cannot be observed until 3 to 4 days of repeated administration. This indicates that, on a pure pharmacokinetic basis, physicians should wait at least 4 days to assess the efficacy of a given dose of u-hFSH and that they should not modify dosage too frequently.


The Quest to Eradicate HPV-Related Oropharyngeal Carcinoma: An Opportunity Not to Miss.
Oropharyngeal squamous cell carcinoma (OPSCC) accounts for more than half of all head and neck cancers. Since the 1970s, OPSCC has shifted from an environmentally triggered to virally mediated disease due to a sharp rise in human papillomavirus (HPV)-related squamous cell carcinoma. Although a highly effective prophylactic vaccine is available, its current implementation is far below national targets, and OPSCC incidence is predicted to further increase by 2045. However, we believe that with prompt action now, we can not only defy these predictions but also effectively eradicate HPV-related OPSCC in these next 20 years. We herein provide an overview of the necessary elements to eliminate this disease: improved primary vaccine uptake, a 1-time universal vaccination effort, and implementation of novel therapeutics that have potential to cure existing disease.


Cancer-specific survival after radical nephroureterectomy for upper urinary tract urothelial carcinoma: proposal and multi-institutional validation of a post-operative nomogram.
Owing to the scarcity of upper urinary tract urothelial carcinoma (UUT-UC) it is often necessary for investigators to pool data. A patient-specific survival nomogram based on such data is needed to predict cancer-specific survival (CSS) post nephroureterectomy (NU). Herein, we propose and validate a nomogram to predict CSS post NU. Twenty-one French institutions contributed data on 1120 patients treated with NU for UUT-UC. A total of 667 had full data for nomogram development. Study population was divided into the nomogram development cohort (397) and external validation cohort (270). Cox proportional hazards regression models were used for univariate and multivariate analyses and to build a nomogram. A reduced model selection was performed using a backward step-down selection process, and Harrell's concordance index (c-index) was used for quantifying the nomogram accuracy. Internal validation was performed by bootstrapping and the reduced nomogram model was calibrated. Of the 397 patients in the nomogram development cohort, 91 (22.9%) died during follow-up, of which 66 (72.5%) died as a consequence of UUT-UC. The actuarial CSS probability at 5 years was 0.76 (95% CI, 71.62-80.94). On multivariate analysis, T stage (P<0.0001), N status (P=0.014), grade (P=0.026), age (P=0.005) and location (P=0.022) were associated with CSS. The reduced nomogram model had an accuracy of 0.78. We propose a nomogram to predict 3 and 5-year CSS post NU for UUT-UC. We have devised and validated an accurate nomogram (78%), superior to any single clinical variable or current model, for predicting 5-year CSS post NU for UUT-UC.


Zinc homeostasis governed by Golgi-resident ZnT family members regulates ERp44-mediated proteostasis at the ER-Golgi interface.
Many secretory enzymes acquire essential zinc ions (Zn2+) in the Golgi complex. ERp44, a chaperone operating in the early secretory pathway, also binds Zn2+ to regulate its client binding and release for the control of protein traffic and homeostasis. Notably, three membrane transporter complexes, ZnT4, ZnT5/ZnT6 and ZnT7, import Zn2+ into the Golgi lumen in exchange with protons. To identify their specific roles, we here perform quantitative Zn2+ imaging using super-resolution microscopy and Zn2+-probes targeted in specific Golgi subregions. Systematic ZnT-knockdowns reveal that ZnT4, ZnT5/ZnT6 and ZnT7 regulate labile Zn2+ concentration at the distal, medial, and proximal Golgi, respectively, consistent with their localization. Time-course imaging of cells undergoing synchronized secretory protein traffic and functional assays demonstrates that ZnT-mediated Zn2+ fluxes tune the localization, trafficking, and client-retrieval activity of ERp44. Altogether, this study provides deep mechanistic insights into how ZnTs control Zn2+ homeostasis and ERp44-mediated proteostasis along the early secretory pathway.


Practolol therapy associated with a systemic lupus erythematosus-like syndrome and an inhibitor to factor XIII.
A patient is described who had an inhibitor to coagulation factor XIII associated with serum autoantibodies to certain tissues. The relationship of these abnormal findings to practolol therapy suggests that this was practolol-induced lupus erythematosus. Further investigations delineating the site of action of the inhibitor to factor XIII are reported.


The role of quantitation of real-time 3-dimensional contrast-enhanced ultrasound in detecting microvascular invasion: an in vivo study.
This study was to evaluate the role of quantitative perfusion analysis of 3-dimensional (3D) contrast-enhanced ultrasound (CEUS) in detecting microvascular invasion (MVI) of liver tumor in vivo. VX2 tumors were implanted in the livers of sixteen New Zealand rabbits. On day 10, real-time 3D CEUS was performed, and the real-time dynamic images were analyzed using online quantification software. The animals were sacrificed and sent for pathology examinations. According to the gold standard of pathology, the animals were divided into an MVI group and a group without MVI (non-MVI group). Time-intensity curves (TICs) were obtained for the VX2 tumors and the surrounding liver parenchyma, and the parameters peak intensity (PI), mean transit time (MTT), and time to peak (TTP) were compared within and between the MVI and non-MVI groups. The TTP and MTT of the VX2 tumors were significantly faster than those of the surrounding liver parenchyma in both MVI and non-MVI groups. The PI of the VX2 tumors was significantly lower than that of the surrounding liver parenchyma in the non-MVI group but not the MVI group. The TTP and MTT of the VX2 tumors and surrounding liver parenchyma were not significantly different in the MVI group compared with the non-MVI group, whereas the ΔPI (the PI ratio between the VX2 liver tumors and the reference liver parenchyma) of the VX2 tumors in the MVI group was larger than that in the non-MVI group. VX2 tumors with MVI present different hemodynamic parameters, with a larger ΔPI than tumors without MVI. Our data suggest that quantitative perfusion analysis of 3D CEUS might be a promising method for predicting MVI in liver tumors.


Identification of a drug degradation product found in a stressed dosage form using LC/MSn, LC/TOF MS and on-line H/D exchange MS.
An unknown degradation product was found when a dosage form was stressed under base and heat. Comprehensive LC-MS studies have been conducted to identify this degradation product. The approach included the use of an ion-trap MS for MS(n) ion fragmentation patterns, a time-of-flight (TOF) MS to measure the accurate mass for its potential chemical formula, and on-line hydrogen/deuterium (H/D) exchange LC-MS to determine the number of exchangeable hydrogen atoms in the gradation product. Based upon the above LC-MS results, the unknown was identified to result from the conversion of a trifluoromethyl moiety in the drug substance to a carboxylic acid under the combination of thermal and base stress. Different ion fragmentation pathways between the drug substance and its degradation product were discussed. The reaction mechanism was proposed to be nucleophilic substitution through S(N)2 mechanism.


Stimulation of nerve growth factor receptors in PC12 by acetyl-L-carnitine.
Acetyl-L-carnitine (ALCAR) prevents some deficits associated with aging in the central nervous system (CNS), such as the aged-related reduction of nerve growth factor (NGF) binding. The aim of this study was to ascertain whether ALCAR could affect the expression of an NGF receptor (p75NGFR). Treatment of PC12 cells with ALCAR increased equilibrium binding of 125I-NGF. ALCAR treatment also increased the amount of immunoprecipitable p75NGFR from PC12 cells. Lastly, the level of p75NGFR messenger RNA (mRNA) in PC12 was increased following ALCAR treatment. These results are in agreement with the hypothesis that there is a direct action of ALCAR on p75NGFR expression in aged rodent CNS.


Correlation between brachial-ankle pulse wave velocity and arterial compliance and cardiovascular risk factors in elderly patients with arteriosclerosis.
The objective of this study was to investigate an association between major cardiovascular risk factors and each of brachial-ankle pulse wave velocity (baPWV), ankle-brachial index (ABI), capacitive arterial compliance (C1), and oscillatory arterial compliance (C2) in elderly patients with arteriosclerosis. We analyzed 160 elderly patients with arteriosclerosis. Vessel wall properties were assessed by baPWV and ABI using a VP-1000 Automatic Arteriosclerosis Measurement System, and C1 and C2 were measured using a DO-2020 Cardiovascular Profiling Instrument. In multiple regression analysis, baPWV was significantly correlated with systolic blood pressure (SBP), mean artery pressure, pulse pressure, diastolic blood pressure (DBP), age, and heart rate (r = 0.670, 0.627, 0.580, 0.523, 0.490, 0.200; p < 0.05), ABI was significantly correlated with pulse pressure, SBP and age (r = -0.250, -0.206, -0.168; p < 0.05), C1 was significantly correlated with pulse pressure, SBP, mean artery pressure, age, DBP and heart rate (r = -0.481, -0.469, -0.363, -0.356, -0.239, -0.188; p < 0.05), and C2 was significantly correlated with age, SBP, pulse pressure, DBP, fasting blood glucose, mean artery pressure and heart rate (r = -0.411, -0.395, -0.383, -0.277, -0.213, -0.183, -0.173; p < 0.05). There were no close correlations between baPWV, ABI, or C1 and fasting blood glucose, total cholesterol, triglycerides, or body mass index. Moreover, there were significant correlations between baPWV and C1 (r = -0.444, p < 0.001), and between baPWV and C2 (r = -0.257, p < 0.01). In conclusion, these findings underscore the efficacy of baPWV and ABI in identifying the vascular damage of the aged.


Optimal timing of examination for acute retrolental fibroplasia.
The records of low birth weight infants who had ophthalmic examination during the first year of life were studied to determine the optimal age at which to screen for retrolental fibroplasia. Fifty-nine cases of RLF were detected in a total of approximately 175 examinations for the birth weight category under 1700 gm during a five-year period. Although about 25% of the initial examinations were performed prior to age 5 weeks, only two cases of RLF were found in that age range. Nine patients found to have a normal peripheral fundus at initial examination, later developed RLF. Since examinations performed during the fourth fortnight of life were 85% positive for RLF, and since retinal detachment in this condition rarely occurs before age 8 weeks, the present series of cases suggests that the optimal time for a single screening examination for RLF is between 7 and 9 weeks of age.


Preclinical discovery and development of maraviroc for the treatment of HIV.
Maraviroc is a first-in-class antiretroviral (ARV) drug acting on a host cell target (CCR5), which blocks the entry of the HIV virus into the cell. Maraviroc is currently indicated for combination ARV treatment in adults infected only with CCR5-tropic HIV-1. This drug discovery case history focuses on the key studies that led to the discovery and approval of maraviroc, as well as on post-launch clinical reports. The article is based on the data reported in published preclinical and clinical studies, conference posters and on drug package data. The profound understanding of HIV's entry mechanisms has provided a strong biological rationale for targeting the chemokine receptor CCR5. The CCR5-antagonist mariviroc, with its unique mode of action and excellent safety profile, is an important therapeutic option for HIV patients. In general, the authors believe that targeting host factors is a useful approach for combating new and re-emerging transmissible diseases, as well as pathogens that easily become resistant to common antiviral drugs. Maraviroc, offering a potent and safe cellular receptor-mediated pharmacological response to HIV, has paved the way for the development of a new generation of host-targeting antivirals.


HepG2 cells predominantly express the type II interleukin 1 receptor (biochemical and molecular characterization of the IL-1 receptor).
In this study we have characterized the cell surface interleukin 1 (IL-1) receptor in HepG2 hepatoma cells. We found that HepG2 cells bind both IL-1 alpha and beta with high affinity, KDs of 136 and 180 pM and receptor densities of 16,000 and 8500 binding sites/cell respectively. The binding sites appeared to be predominantly type II since phorbol ester treatment of the cells, which selectively downregulates type II IL-1 receptors, reduced binding by 68% while treatment of the cells with an inhibitory monoclonal antibody specific for the type I receptor had no significant effect on IL-1 binding. Competition studies with a modified IL-1 beta analog (Glu4) also revealed binding kinetics more consistent with binding to type II receptors than to type I. Crosslinking and ligand blotting with human 125I-IL-1 demonstrated the presence of two bands, a 78 kDa band typical of crosslinking to type II (p60) receptor, and a 98 kDa band, typical of crosslinking to the type I (p80) receptor. Low level expression of the type I receptor was consistent with molecular biological studies employing polymerase chain reaction (PCR) amplification which indicated that mRNA for the type I receptor was produced by the HepG2 cells. Functional receptors were demonstrated by the induction of IL-8 by IL-1 stimulated cells.


The current neurologic burden of illness and injury in the United States.
Estimates of the need for neurologists must be based ultimately on the frequency of neurologic disease. Community-based population surveys for diseases or injuries that have come to medical attention provide annual incidence rates per 100,000 population, point prevalence rates per 100,000, and average duration in years. For 61 disorders, including for 8 only those fractions that were thought to require neurologic attention, the annual incidence rates summed to 2500 per 100,000 or 2.5% of the population. For 55 of these conditions, including for 6 only the neurologic fraction and excluding all mental retardation, blindness, deafness, or psychosis, the point prevalence rates summed to 9500 per 100,000 population. Even if we also excluded all headache, all trauma, all alcoholism, and all vertebrogenic pain states, 3.6% of the general population at any one time should be under neurologic care. Substracting all these exclusions from the incidence rates similarly leaves more than 1 person in every 100 who each year will have a new neurologic disorder that requires the attention of a physician competent in clinical neurology.


Efficacy of weekly paclitaxel in patients with advanced gastric cancer refractory to docetaxel-based chemotherapy.
Only partial cross-resistance between docetaxel and paclitaxel has been demonstrated in breast and ovarian cancers. Whether weekly paclitaxel is effective in patients with advanced gastric cancer refractory to docetaxel-based chemotherapy remains unclear, and we aimed to clarify the efficacy and safety of weekly paclitaxel in such patients. Patients who had received docetaxel-based regimens were assigned to the prior-docetaxel group, and those who had never received docetaxel were designated as the non-docetaxel group. Paclitaxel at 80 mg/m(2) was administered by intravenous infusion in all patients, and this was repeated weekly for 3 weeks out of 4. Between April 2006 and June 2011, 65 patients were studied: 26 in the prior-docetaxel group and 39 patients were non-docetaxel group. The median age, gender, performance status, histological type, history of gastrectomy, and the locations and numbers of metastatic sites did not differ significantly between the two groups. In the prior-docetaxel group, the response rate (RR) was 14.2% (3/21) among patients with measurable lesions, median progression-free survival (PFS) was 79 days [95% confidence interval (CI), 47-135 days], and overall survival (OS) was 123 days (95% CI, 90-215 days) from the initiation of paclitaxel treatment. In the non-docetaxel group, the RR was 11.5% (3/26) among patients with measurable lesions, PFS was 82 days (95% CI, 52-106 days), and OS was 143 days (95% CI, 121-178 days). The efficacy of weekly paclitaxel thus appeared to be similar in the two groups. Weekly paclitaxel was modestly active in patients with gastric cancer refractory to docetaxel-based chemotherapy.


Genomic heterogeneity in myeloproliferative neoplasms and applications to clinical practice.
The myeloproliferative neoplasms (MPN) polycythaemia vera, essential thrombocythaemia and primary myelofibrosis are chronic myeloid disorders associated most often with mutations in JAK2, MPL and CALR, and in some patients with additional acquired genomic lesions. Whilst the molecular mechanisms downstream of these mutations are now clearer, it is apparent that clinical phenotype in MPN is a product of complex interactions, acting between individual mutations, between disease subclones, and between the tumour and background host factors. In this review we first discuss MPN phenotypic driver mutations and the factors that interact with them to influence phenotype. We consider the importance of ongoing studies of clonal haematopoiesis, which may inform a better understanding of why MPN develop in specific individuals. We then consider how best to deploy genomic testing in a clinical environment and the challenges as well as opportunities that may arise from more routine, comprehensive genomic analysis of patients with MPN.


Ethics, engineers and drama.
This paper describes four plays which illustrate ethical themes relevant to engineers and which could be used as a resource for engineers who wish to explore ethical topics and their relationship with professional practice. The plays themselves have been chosen because a character in the play is involved in engineering activities. Each play is analysed to highlight some of the ethical issues the play raises. Often ethical topics are presented in abstract terms but the plays relate ethical issues to individuals and individual actions in specific situations that connect either directly or figuratively to practical situations engineers find themselves in. The paper describes how the resources have or could be used in an educational programme.


Functional and structural similarities between protease nexin I and C1 inhibitor.
Protease nexin I is a proteinase inhibitor that is secreted by human fibroblasts and forms stable complexes with certain serine proteinases; the complexes then bind to the fibroblasts and are rapidly internalized and degraded. In this report, we show that this inhibitor, which is present in very low concentrations in plasma, has functional and structural similarities to C1 inhibitor, an abundant proteinase inhibitor in plasma. Both inhibitors complex and inactivate certain proteinases that previously were known to rapidly react only with C1 inhibitor. Kinetic inhibition studies show that protease nexin I inhibits Factor XIIa and plasma kallikrein with second-order rate constants of 2.3 x 10(3) and 2.5 x 10(5) M-1 s-1, respectively, which are similar to the rate constants for inhibition of these proteinases by C1 inhibitor. Protease nexin I inhibits C1s about one-tenth as rapidly as does C1 inhibitor. Alignment of the amino acid sequences of protease nexin I and C1 inhibitor shows that these proteins have similarity at their reactive centers (from sites P7 to P1). The remaining regions of the two proteins share much less similarity. In contrast to protease nexin I, C1 inhibitor is not secreted by human fibroblasts. Although 125I-C1s-protease nexin I complexes readily bind to human fibroblasts, binding of 125I-C1s-C1 inhibitor complexes or other 125I-proteinase-C1-inhibitor complexes to these cells is not detectable. Thus, protease nexin I and C1 inhibitor may control some common regulatory proteinases in the extravascular and vascular compartments, respectively.


Osteochondritis Dissecans of the Humeral Capitellum in Young Athletes: Comparison Between Baseball Players and Gymnasts.
Osteochondritis dissecans (OCD) lesions are often observed in the humeral capitellum both in young baseball players and gymnasts. It is generally believed that capitellar OCD in baseball players can be seen on an anteroposterior (AP) radiograph with the elbow in 45° of flexion. However, the mechanism of injury seems to be different in baseball players and gymnasts. Repetitive valgus overload with the elbow in flexion is believed to be the cause of capitellar OCD lesions in baseball players, whereas weightbearing with the elbow in extension may be the cause of OCD in gymnasts. To determine the difference in capitellar OCD location between baseball players and gymnasts and to propose the optimal AP radiographic angle of the elbow for visualization of early-stage OCD lesions in adolescent gymnasts. Cross-sectional study; Level of evidence, 3. Subjects consisted of 95 baseball players (95 elbows) and 21 gymnasts (24 elbows) with a mean age of 13.7 years (range, 11-18 years). To localize the lesion, inclination of the affected area in the humeral capitellum against the humeral axis was investigated using sagittal computed tomography images of the elbow. The inclination angle was defined as the angle between the long axis of the humerus and the line perpendicular to a line that connected the anterior and posterior margin of the lesion. The inclination angle in each group was compared and statistically analyzed. The mean inclination angle was 57.6° ± 10.7° in baseball players and 28.0° ± 10.7° in gymnasts. Capitellar OCD lesions were located more anterior in baseball players when compared with gymnasts (P < .01). Due to differences in applied stress, capitellar OCD lesions in baseball players were located more anteriorly compared with those seen in gymnasts. Therefore, although AP radiographs with the elbow in 45° of flexion are optimal for detecting OCD lesions in baseball players, radiographs with less elbow flexion or full extension are more useful in gymnasts, especially in early-stage OCD.


Platelet functions in patients with aortic ball valves.
Platelet functions were studied in normal subjects and patients with single Staff-Edwards aortic ball valves of series 1200 and 2300. The most pronounced changes were found in platelet adhesiveness, measured with Hellem's modified method. The mean percentage of adhesive platelets was reduced from 71.8 in normal subjects to 50.9 in patients with valve type 1200 and to 27.2 in those with type 2300. An inverse correlation was found between platelet adhesiveness and the degree of intravascular hemolysis, as reflected by serum LDH levels. The mean bleeding time was significantly prolonged in patients with valve 2300, and the individual values correlated inversely to the adhesiveness. The mean values of platelet counts, or irreversible aggregation induced by collagen or epinephrine, and of platelet survival were all moderately-but significantly-reduced as compared to normal. The most important mechanism behind the disturbed platelet reactivity is probably mechanical damage of the platelets by the valve, whereas refractoriness of platelets toward ADP liberated from red cells as well as consumption of adhesive platelets by thrombus formation is thought to have limited influence on platelet behavior. Platelet function was altered to the same extent in patients with a history of arterial thromboembolic complications as in those without. The disturbed platelet reactivity may predispose to bleeding, but may also offer some protection against arterial thromboembolism.


A three-dimensional finite element analysis of the sports mouthguard.
The aim of this study was to evaluate the compressive and tensile stresses on dentin and enamel in five different situations: no mouthguard and mouthguards from 1 mm thickness up to 4 mm thickness, using finite element analysis. A three-dimensional geometry of an upper right central incisor was obtained from a computed tomography and transformed into a mesh separating enamel from dentin. A mouthguard was created covering the buccal surface of the enamel in different thicknesses, and a rubber ball with a velocity of 5 m s(-1) was made as the impact object. The maximum principal stress and the minimal principal stress were evaluated in all situations on dentin and enamel. Both maximum and minimal stress on enamel had the greatest value on the control situation (no mouthguard), and their value decreased as the mouthguard thickness increased. The reduction ranged from 66.62% to 85.5% for compressive stress and from 9.76% to 33.37% for tensile stress on enamel. The results for dentin were similar among the situations with or without mouthguards. The mouthguard had beneficial effect considering the stresses on enamel, and between the mouthguard thickness of 3 and 4 mm, there was minimum difference.


The Influence of the Socioeconomic Status and the Density of the Population on the Outcome After Peripheral Artery Disease.
Low socioeconomic status (SES) and living in a rural environment are associated with poorer health and a higher number of amputations among the population at large. The purpose of this study is to determine the influence of low SES and of the degree of urbanization on the short-term and long-term results of patients after revascularization for peripheral artery disease. An observational retrospective follow-up study of 770 patients operated on for peripheral artery disease at three university centers in north-western Spain from January 2015 to December 2016. The events studied were Rutherford classification of severity upon admission, direct amputation, amputations in the follow-up period, new revascularization procedures, major adverse cardiovascular events (MACE), and overall mortality. Mean personal income and income of the household associated with the street in which each patient lived and the degree of urbanization in three areas as per Eurostat criteria: densely populated areas, intermediate density areas, and thinly populated areas. Comorbidity, surgical, and follow-up variables were also collected. Descriptive analysis and Cox regression were used. Approval was obtained from the regional ethics committee. Median follow-up was 47.5 months. MACE occurred in 21.5% of the series and overall mortality was 47.0%. Living in a thinly populated area is associated with a lower risk of MACE (adjusted subhazard ratio = 0.60; 95% confidence interval [CI]: 0.39-0.91). Overall survival is lower in intermediate density area patients (adjusted Hazard Ratio = 1.46; 95% CI: 1.07-2.00). The third quartile of mean personal and household income is associated with a higher risk of major amputation at follow-up (adjusted Odds Ratio 1.92, 95% CI: 1.05-3.52 and adjusted Odds Ratio 1.93, 95% CI: 1.0.3-3.61, respectively). Patients who live in a densely populated area run a higher risk of MACE. SES is neither associated with worse outcomes after surgery nor with MACE in long-term follow-up.


Infiltrative solid papillary carcinoma of the breast with axillary lymph node metastasis: a case report.
Solid papillary carcinoma (SPC) is a rare breast papillary tumor variant. The main histological features of SPC consist of neoplastic cell-rich nodules with thin fibrovascular cores, often accompanied by mucous secretion and neuroendocrine differentiation. Infiltrative solid papillary carcinoma (ISPC) tumor cells have an invasive, map-like growth pattern with serrated irregular growth. Due to its unique clinicopathological features, SPC is classified as two pathological tissue types based on the 2019 WHO classification of breast tumors: SPC in situ and ISPC. We report a case of a 55-year-old female patient who was admitted to the hospital due to a painless left breast mass that had persisted for two years. Mammography suggested a mass in the left upper outer quadrant (BI-RADS 4B), and ultrasound of the breast demonstrated a cystic mass of the left breast (US_BI_RADS 4 C) with multiple enlarged lymph nodes in the left axilla. Postoperative pathology revealed ISPC with one lymph node metastasis in the left breast. Modified radical mastectomy was performed on the left breast. Subsequently, the patient received letrozole endocrine therapy, epirubicin hydrochloride and cyclophosphamide chemotherapy, and radiotherapy of the left chest wall and left upper and lower clavicular regions. After 17 months of follow-up, there was no evidence of recurrence or distant metastasis. SPC is a group of heterogeneous tumors. SPC in situ has a good prognosis. In contrast, ISPC has a unique histological morphology and growth pattern with invasive biological behavior that can lead to lymph node and distant metastases.


Selective management of abdominal and thoracic stab wounds with established peritoneal penetration: the eviscerated omentum.
In a prospective study involving 276 patients, stab wounds to the abdomen and lower chest with certain penetration into the peritoneal cavity were managed selectively. On the basis of physical findings, patients underwent either immediate laparotomy or close observation with frequent reexaminations and operation only if signs changed. The reliability of physical examination and the safety of nonoperative treatment in the absence of peritoneal signs were assessed. The overall incidence of major damage, including damage to the diaphragm, was 59.1 percent. Significant intraperitoneal visceral injury was found in 45.7 percent of patients with transabdominal stab wounds and in 25 percent of those with transthoracic stab wounds. Physical examination correctly predicted the findings in 90 to 96 percent of patients at initial assessment, with a sensitivity of 88.4 percent and a specificity of 93.9 percent. As delayed laparotomy after a change in signs during observation did not increase morbidity or hospital stay, and the unnecessary laparotomy rate in this study was 5.9 percent, we recommend a policy of selective management of abdominal and thoracic stab wounds with omental evisceration or other evidence of peritoneal penetration. Local wound care with amputation of the protruded omentum followed by close observation and monitoring of vital signs is safe surgical practice when no peritoneal signs or other indication for urgent exploration are present on admission.


Factors associated with endometrial bleeding in continuous hormone replacement therapy.
To identify clinical and laboratory parameters associated with the occurrence of endometrial bleeding within the first 6 months of treatment in postmenopausal women taking continuous hormone replacement therapy. We performed a prospective study of 55 postmenopausal women who had amenorrhea for at least 12 months before baseline screening and were taking 0.625 mg conjugated estrogen and 5 mg medroxyprogesterone acetate daily on a continuous basis. Postmenopausal duration was defined as the interval, in months, between the last menstruation and the commencement of treatment. All subjects were instructed to monitor bleeding episodes in a diary and were followed up monthly for at least 12 months. Thirty-four women (62%) experienced bleeding within the first 6 months of treatment. Using a multivariate approach, a woman with a postmenopausal duration of 24 months or less had a relative risk of 8.2 (95% confidence limits: 1.3, 53.1) of bleeding, as compared with those with a postmenopausal duration of more than 24 months. Furthermore, pretreatment endometrial thickness greater than 5 mm (p < 0.05) and serum estradiol levels greater than 25 pg/mL (p < 0.01) were noted to be significantly correlated with the occurrence of bleeding in women with a postmenopausal duration of more than 24 months. Women with a postmenopausal duration of 24 months or less, a pretreatment endometrial thickness greater than 5 mm, and serum estradiol level greater than 25 pg/mL are at risk to have endometrial bleeding within the first 6 months of continuous hormone replacement therapy.


Early effect of growth factors (EGF + insulin) upon ATP turnover in 3T3 cells.
Various early biochemical events have been observed after the addition of growth factors to quiescent cultures of 3T3 cells; however, the cascade of events which take place in the cells after growth-factor addition is not yet entirely known. Our results show that the addition of a mixture of two growth factors, i.e., Epidermal Growth Factor (EGF) and insulin, to quiescent cultures of 3T3 cells rapidly stimulated phosphate uptake and ATP turnover. Our present and previous results suggest that the increase in phosphate uptake is the consequence of the stimulation of ATP synthesis. This stimulation was not simply a consequence of an increase in oxidative phosphorylation or in glucose transport and metabolism. The change in ATP turnover was an early event observed as soon as 5 min after growth-factor addition; furthermore, it was not dependent on protein synthesis. This change may therefore be the result of post-synthetic modification of enzymes by phosphorylation. We do not know what cellular process is responsible for the increase in ATP turnover. Since growth-factor addition rapidly enhanced ATP degradation in quiescent 3T3 cell cultures, we assumed that this increase is the result of an increase in ATP degradation. We know that it was not due to a stimulation of an oligomycin-sensitive ATPase. We verified that it was not the consequence of early biochemical events like an increase in Na+/K+ ATPase or a stimulation of RNA or protein synthesis. However, it is of interest to note that the stimulation of ATP turnover due to the growth-factor addition was inhibited by quercetin.


Resident Rounds: Part III - Case Report: Betel Quid Induced Irritant Contact Dermatitis of the Hand.
Betel quid is a drug used in Far East Asia, India, and the South Pacific. The habit of betel quid chewing is widely reported to cause oral cancer and tooth and gum disease. However, skin disease due to betel quid use is underreported. We report a case of irritant contact dermatitis to betel quid components in a 35-year-old male betel quid user who presented for evaluation of a persistent rash on his fingertips.


Validation and comparison of the psychometric properties of the EQ-5D-3L and EQ-5D-5L instruments in Greece.
To validate and compare the psychometric properties of the EQ-5D-3L with the EQ-5D-5L classification systems in Greece. Participants (n = 2279) over 40 years old, sampled from the greater area of Athens using a multistage stratified quota sampling method, completed both EQ-5D versions, while information was also collected on socio-demographics and health-related characteristics. The EQ-5D-5L and EQ-5D-3L were evaluated in terms of agreement, ceiling effects, redistribution and inconsistency, informativity, and convergent and known-groups validity. The agreement between the EQ-5D-3L and EQ-5D-5L was high (ICC = 0.85). Ceiling effects decreased significantly in the EQ-5D-5L in all domains (P < 0.001), with "usual activities" (-21.4 %) and "self-care" (-20.1 %) showing the highest absolute and "anxiety/depression" the highest relative reduction (-32.46 %). Inconsistency was low (5.7 %). The increase in prevalence of problems was larger than the decrease in their severity, resulting in a lower mean health utility for the EQ-5D-5L. Overall absolute and relative informativity improved by 70.5 % and 16.4 %, respectively, in the EQ-5D-5L. Both instruments exhibited good convergent and known-groups validity, with evidence of a considerably better convergent performance and discriminatory ability of the EQ-5D-5L. Both EQ-5D versions demonstrated good construct validity and had consistent redistribution. The EQ-5D-5L system may be preferable to the EQ-5D-3L, as it exhibited superior performance in terms of lower ceiling effects, higher absolute and relative informativity, and improved convergent and known-groups validity efficiency.


Effect of injected dexamethasone on relative cytokine mRNA expression in bronchoalveolar lavage fluid in horses with mild asthma.
Mild equine asthma is a common inflammatory airway disease of the horse. The primary treatment of mild equine asthma is corticosteroids. The purpose of this study was to investigate the effects of injected dexamethasone on relative IL-1β, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p35, IL-17, IL-23, IFN-γ, Eotaxin-2 and TNF-α mRNA expression in bronchoalveolar lavage (BAL) fluid in healthy Thoroughbred horses (n = 6), and those with mild equine asthma (n = 7). Horses with mild equine asthma had a significantly greater bronchoalveolar lavage mast cell percentage than healthy horses both before and after treatment. Mild equine asthma was associated with a 4.95-fold up-regulation of IL-17 (p = 0.026) and a 2.54-fold down-regulation of IL-10 (p = 0.049) compared to healthy horses. TNF-α was down-regulated in response to dexamethasone treatment in both healthy horses (3.03-fold, p = 0.023) and those with mild equine asthma (1.75-fold, p = 0.023). IL-5 was also down-regulated in horses with mild asthma (2.17-fold, p = 0.048). Horses with mild equine asthma have a lower concentration of IL-10 in BAL fluid than healthy controls which concurs with human asthmatics. The marked up-regulation of IL-17 in horses with mild asthma suggests these horses had a true tendency of "allergic" airway inflammation in response to environmental allergens. Dexamethasone administration exerted anti-inflammatory effects associated with down-regulation of TNF-α in all horses, and decreased levels of IL-5 mRNA expression in horses with mild equine asthma. The inhibition of the Th-2 response, without any alterations to the airway cytology, indicates that maintained exposure to environmental allergens perpetuates airway inflammation.


Forearm interosseous membrane trauma: MRI diagnostic criteria and injury patterns.
Define criteria for interosseous membrane (IOM) injury diagnosis using MRI, and characterize patterns of IOM disruption following forearm trauma. Our hypothesis is that most IOM injuries occur along the ulnar insertion, and MRI should be obtained following forearm trauma to assess IOM competency. Sixteen cadaver forearms were subjected to longitudinal impact trauma. Prior to and following injury, MR images were examined by a board-certified musculoskeletal radiologist using pre-defined criteria for determining IOM integrity. Each specimen was dissected and the viability/pattern of injury examined. The MRI and dissection results were compared using a double-blinded methodology. Eight of the 16 specimens demonstrated IOM trauma. Seven specimens demonstrated complete IOM disruption from the ulnar insertion, and one revealed a mid-substance tear with intact origin and insertion. The dorsal oblique bundle was disrupted in four specimens. MRI analysis identified IOM injury in seven of the eight forearms. The injury location was correctly identified in six specimens when compared to dissection observations. MRI determination of IOM injury demonstrated a positive predictive value of 100%, a negative predictive value of 89%, a sensitivity of 87.5% and a specificity of 100%. Our findings demonstrate the accuracy of MRI in identifying IOM disruption, and its ability to localize specific injuries in a clinically relevant model of forearm trauma. The injury patterns demonstrated most lesions occurred along the IOM's ulnar insertion, and in half of the injured specimens there was concomitant dorsal oblique bundle disruption.


[Regulating pre-antral follicle development: a brake on depletion of the ovarian reserve].
The process of folliculogenesis is a complex and dynamic process that is regulated by positive and negative factors. During folliculogenesis in the mammalian ovary, the primordial follicle pool is gradually reduced through successive waves of follicle growth. It is important that this pool is carefully regulated, otherwise premature ovarian failure will occur. This process results in the ovulation of an ovocyte or more commonly, the loss of ovocytes through atresia. The majority of research has concentrated on the positive regulators of follicle growth with very little attention on the negative regulators. Nonetheless, there are several factors that have been observed to inhibit follicle activation and development. In this review, we summarize those here.


Phosphatidic and lysophosphatidic acid production in phospholipase C-and thrombin-treated platelets. Possible involvement of a platelet lipase.
Incubation of 32P-labelled platelets with Clostridium welchii phospholipase C greatly stimulates 32P-incorporation into phosphatidic and lysophosphatidic acids. A net synthesis is demonstrated for both phospholipids, which exhibit identical specific radioactivities. Phosphatidic acid production roughly parallels the phospholipase C-induced aggregation, whereas lysophosphatidic acid appears secondarily during cell lysis. The same qualitative variations are observed during thrombin-induced aggregation. At the physiological pH used throughout the incubations, platelets display no phospholipase A activity towards phosphatidic acid, whereas diglycerides are deacylated by platelet lysates. On the basis of these findings, a mechanism for phosphatidic and lysophosphatidic acid production is proposed, involving a phosphorylation of the di- and monoglycerides formed upon phospholipase C and lipase action. The possible role of such a pathway in regulating arachidonic acid release from phospholipids during platelet activation is discussed.


Epilepsy surgery: perioperative investigations of intractable epilepsy.
Recent advances in our understanding of the basic mechanisms of epilepsy have derived, to a large extent, from increasing ability to carry out detailed studies on patients surgically treated for intractable epilepsy. Clinical and experimental perioperative studies divide into three different phases: before the surgical intervention (preoperative studies), on the intervention itself (intraoperative studies), and on the period when the part of the brain that has to be removed is available for further investigations (postoperative studies). Before surgery, both structural and functional neuroimaging techniques, in addition to their diagnostic roles, could be used to investigate the pathophysiological mechanisms of seizure attacks in epileptic patients. During epilepsy surgery, it is possible to insert microdialysis catheters and electroencephalogram electrodes into the brain tissues in order to measure constituents of extracellular fluid and record the bioelectrical activity. Subsequent surgical resection provides tissue that can be used for electrophysiological, morphological, and molecular biological investigations. To take full advantage of these opportunities, carefully designed experimental protocols are necessary to compare the data from different phases and characterize abnormalities in the human epileptic brain.


A 'tête-à tête' between cancer stem cells and endothelial progenitor cells in tumor angiogenesis.
Accumulating evidence suggests the involvement of stem cells in tumor angiogenesis. Two major types of stem cells frequently discussed in this regard are bone marrow-derived endothelial progenitor cells (EPCs) and tumor-derived cancer stem cells (CSCs). The present review discusses the possibility of a close association between these two cell types that drives the tumor towards metastasis. An exploration of this plausible relationship between EPCs and CSCs is imperative to completely unveil the mechanisms of tumor angiogenesis and develop CSC- and/or EPC-targeted anti-tumor therapies.


Recent Progress in the Discovery and Development of TRPA1 Modulators.
TRPA1 is a well-validated therapeutic target in areas of high unmet medical need that include pain and respiratory disorders. The human genetic rationale for TRPA1 as a pain target is provided by a study describing a rare gain-of-function mutation in TRPA1, causing familial episodic pain syndrome. There is a growing interest in the TRPA1 field, with many pharmaceutical companies reporting the discovery of TRPA1 chemical matter; however, GRC 17536 remains to date the only TRPA1 antagonist to have completed Phase IIa studies. A key issue in the progression of TRPA1 programmes is the identification of high-quality orally bioavailable molecules. Most published TRPA1 ligands are commonly not suitable for clinical progression due to low lipophilic efficiency and/or poor absorption, distribution, metabolism, excretion and pharmaceutical properties. The recent TRPA1 cryogenic electron microscopy structure from the Cheng and Julius labs determined the structure of full-length human TRPA1 at up to 4Å resolution in the presence of TRPA1 ligands. This ground-breaking science paves the way to enable structure-based drug design within the TRPA1 field.


PRL and ACTH secretion following acute heat exposure, in intact and in hypothalamic deafferentated male rats.
Adult male rats, intact or bearing complete, anterior or posterior hypothalamic deafferentiations (CHD, AHD AND PHD, respectively) were acutely exposed to environmental temperature of 36 degrees C, and serum PRL and ACTH concentrations were determined by RIA. In intact animals, heat exposure resulted in elevated serum PRL and ACTH levels. None of the deafferentations affected basal serum PRL concentrations, whereas those of ACTH were elevated in both CHD and AHD, but not in PHD groups, as compared to intact controls. The PRL heat response was completely absent in CHD, attenuated in AHD, and delayed in PHD animals, and the ACTH heat response was absent in all three groups. These results demonstrate (1) that acute exposure to elevated environmental temperature stimulates secretion of PRL and of ACTH; (2) that this stimulation is carried out by diverse neural pathways; and, (3) that hypothalamic modulation of the secretion of PRL and ACTH is effected by independent mechanisms.


Plasma levels of active and total ghrelin in renal failure: a relationship with GH/IGF-I axis.
Ghrelin was originally isolated from the rat stomach and significant amounts were found also in the kidney. Present study was designed to examine changes in ghrelin levels in renal failure and their relationship to the GH/IGF-I axis. Fourty patients with mild-to-severe CRF (19 men, 21 women, aged 62.5 +/- 2.2 years, BMI 27.57 +/- 0.73 kg/m(2)) and 34 healthy control subjects (17 men, 17 women, aged 60 +/- 2.6 years, BMI 27.55 +/- 0.79 kg/m(2)) were included in the study. Total ghrelin levels were significantly increased in patients with chronic renal failure (CRF) (p < 0.0001). Total ghrelin in CRF correlated positively with active ghrelin (p < 0.001), GH (p < 0.05), IGF-I (p < 0.05), free IGF-I (p = 0.0001), IGFBP-3 (p < 0.01), IGFBP-2 and -6 (p < 0.05). Active ghrelin in CRF correlated positively with IGF-I (p < 0.001), free-IGF-I (p < 0.005), IGFBP-2 (p < 0.05) and IGFBP-3 (p < 0.05). However, most of the correlation were markedly reduced and the significance disappeared after adjustment for different creatinine levels. Hemodialysis in patients with end stage renal disease (ESRD) resulted in a significant reduction of plasma total and active ghrelin (p < 0.01 and p < 0.001 respectively). In conclusion we demonstrated elevated plasma levels of total ghrelin in CRF, and a reduction of total and active ghrelin after a single course of hemodialysis in ESRD. The elevation of ghrelin levels could be caused by impaired clearance and/or metabolism of ghrelin in the kidney. We did not prove clearly significant relationship between ghrelin serum levels and parameters of GH/IGF-I axis in study subjects.


Phytochemical profile of seeds from 21 Bambara groundnut landraces via UPLC-qTOF-MS.
Bambara groundnut is one of the under-utilized African legume crops, valued for its nutritional and health benefits, and for which ongoing studies will help to distinguish its many landraces and select the promising one for breeding programs. To describe the polar metabolome of the seed from 21 Bambara groundnut landraces, untargeted metabolomics approach using UPLC-qTOF-MS (Ultra performance liquid chromatography-Quadrupole time of flight mass spectrometry) was performed. Metabolites belonging to varied compound classes were detected and identified. The total phenolic, flavonoid and anthocyanin contents varied from 0.75 to 17.71 mg GAE.g-1, 0.01 to 2.51 mg QUE.g-1 and 0.03 to 1.31 mg CYE.g-1, respectively. Unsupervised statistics highlighted differences in the metabolome of different landraces. Principal component analysis revealed that caffeic and catechin conjugates are the most decisive marker compounds discriminating the landraces. This study provides the most complete map of metabolites in Bambara groundnut seeds and demonstrates that UPLC-qTOF-MS coupled with chemometric is an excellent tool for differentiation between landraces. These findings highlight the potential of Bambara groundnuts as an economic source of natural antioxidants for human consumption and food industries, and therefore open horizons to the industrial use of Bambara groundnut flours in the development of functional food and feed products.


The health effects of wastewater on the prevalence of ascariasis among the children of the discharge zone of El Jadida, Morocco.
Proximity to wastewater constitutes an infection hazard by ascariasis. This is supported by the results of an epidemiologic study of a group of children living near an area of wastewater effluents. The subjects of this study were schoolchildren from Sidi Daoui, a neighborhood located in the area of the main effluent of the city of El Jadida, Morocco. For a comparative approach, a control group was selected from Sidi Moussa, a neighborhood far from the discharge area. The incidence of ascariasis was 18.1% in the study group (Sidi Daoui) and 1% in the control group (Sidi Moussa). It was found that 71% of the exposed children were suffering from acute parasitic infections. The risk attributable to wastewater in transmitting ascariasis to examined children in Sidi Daoui was about 17%. Boys, particularly those aged 7 - 10, appeared to be the most vulnerable to contracting ascariasis. This study demonstrates the relationship between ascariasis in children and their proximity to wastewater effluents.


Database for queries of melanoma cohorts with molecular and clinical data.
Large genome-scale studies are deposited in various public sequence repositories. However, their access and analysis can be non-trivial to infrequent users. Here, we present a new database connecting whole transcriptomes with clinical data for straight-forward access and analysis of patient-specific samples. Users can perform association tests of survival and gene expression across different cohorts, identify cell-type expressions, or correlate the presence of immune cells. In summary, we present a new data hub for bench scientists to perform replication and discovery studies.


Influencing health behaviour using smart building interventions for people with dementia and mild cognitive impairment: expert interviews and a systematic literature review.
Behaviour can have an influence on (coping with) chronic conditions such as dementia. Assistive technology can stimulate the daily behaviour of people with dementia, but the mechanisms through which this happens are unclear. Therefore, this paper focuses on potential behaviour change mechanisms, that can be employed in smart building interventions for people with dementia or MCI. This research uses expert interviews with medical experts (n = 9) and a systematic literature review of smart building interventions stimulating health behaviour (n = 12). Results show how facilitation, incentive motivation (i.e., feedback), observational learning and self-efficacy are most promising according to medical experts; if they are appropriately personalised towards needs, preferences as well as abilities. The literature review shows how most of the examined research uses facilitation and incentive motivation to stimulate behaviour. Although positive results are reported in all studies, methodological quality could be improved. For the design of smart building interventions for people with MCI or dementia, facilitation and incentive motivation seem to be promising behaviour change mechanisms. Outcome expectation, observational learning and self-efficacy could reinforcing the aforementioned mechanisms. Future research should focus on how different (environmental, digital) cues can be personalized and can adapt over time, as dementia progresses.IMPLICATIONS FOR REHABILITATIONAssistive technology for people with dementia can have an effect on (health) behaviour, which may in turn influence coping strategies or quality of life.Behaviour change mechanisms can inform the design of assistive technology such as smart building interventions.Facilitation, Incentive Motivation, Observational Learning and Self-efficacy seem promising behaviour change mechanisms for people with dementia or MCI.In any intervention for people with dementia, personalized and adaptable cues are of vital importance.


Evaluation of analgesic efficacy of superficial cervical plexus block in patients undergoing modified radical mastoidectomy: A randomised controlled trial.
Intravenous analgesics and local infiltration are used for postoperative analgesia in patients undergoing mastoidectomy. No randomised controlled trial (RCT) has so far determined response rates of pain reduction after ultrasound-guided superficial cervical plexus block (SCPB) in adult patients undergoing modified radical mastoidectomy. This double-blind RCT was conducted in 30 adult patients of the American Society of Anesthesiologists (ASA) grade I/II undergoing modified radical mastoidectomy. The primary outcome was a reduction in the visual analogue scale (VAS) score. Secondary outcomes were postoperative diclofenac consumption, haemodynamics, and occurrence of any adverse events. All patients received general anaesthesia. At the end of the surgery, patients were randomised to either Group 'Block' (n = 15) ultrasound guided SCPB with 5 mL ropivacaine 0.5% or Group 'No block' (n = 15). All patients received intravenous (IV) paracetamol 1 g every 6 hourly and rescue analgesic IV diclofenac 75 mg if VAS score >4. Patients in Group 'Block' reported lower VAS score at rest versus Group 'No block' at 1 h postoperatively (P = 0.012). VAS score on movement was lower in patients of Group 'Block' compared to Group 'No block' at 1 h (P = 0.010), 4 h (P = 0.035), 8 h (P = 0.027), and 12 h (*P = 0.003) postoperatively. Diclofenac consumption was lower in patients of Group 'Block' (P = 0.041). No adverse effects were reported. Postoperative ultrasound-guided SCPB produced higher response rates in terms of reduction in VAS score in patients undergoing modified radical mastoidectomy.


Microtubules observed within the cistern of RER in neurons of the aged dog.
Twenty-seven randomly selected dogs ranging from 1 month to 16 years of age were examined light- and electron microscopically. An intraneuronal inclusion body was found im 13 of 27 cases. In particular, 12 of 13 positive cases were elderly dogs of over 8 years of age. The inclusions showed amphophilic violet color with H.-E. stain and measured 3--42 micrometer in diameter. Histochemically, they were thought to be a glycoprotein complex. The inclusions were characterized by the electron microscopy and composed of aggregated cistern of RER closely packed with tubular structures. The individual tubules measured about 24 nm in diameter and had 11--13 subunits forming their walls. These constituents were very similar to those of microtubules. The occurrence of the inclusion bodies showed an apparent age-dependency.


Sleep complaints, depression and quality of life in Norwegian dialysis patients.
This study explores sleep problems in dialysis patients and the associations to health-related quality of life (HRQoL) and depression. A comparison between different validated sleep questionnaires was done in order to find an appropriate diagnostic tool in clinical practice. In a cross-sectional study of 301 prevalent dialysis patients, sleep problems were elaborated with Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS). Poor sleep was defined as PSQI score > 5 and daytime sleepiness as ESS > 10. HRQoL, including quality of sleep, was evaluated with the Kidney Disease and Quality of Life - Short Form (KDQoL-SF), and physical (PCS) and mental component summary scores (MCS) were computed. Depression was assessed with Beck Depression Inventory (BDI). Poor sleep and excessive daytime sleepiness was found in 74.3% and 22.2%, respectively. Depression was common (29.5%) and associated with reduced sleep quality (ρ = 0.49, p < 0.001). Poor sleepers had significantly lower MCS (51.8 ± 9.6 vs. 46.6 ± 10.6, p = 0.001) and PCS (41.8 ± 9.6 vs. 35.2 ± 10.0, p < 0.001) compared to good sleepers. PSQI scores were independently associated with PCS (p = 0.001), but not MCS (p = 0.468) in multivariate analyses. The sleep subscale from KDQoL-SF was strongly correlated to PSQI (r = -0.75, p < 0.001). As sleep complaints, daytime sleepiness and depression were prevalent, all dialysis patients should routinely be screened for self-perceived sleep problems with a simple Questionnaire.


Seasonal and spatial variations in the phytoplankton community and their correlation with environmental factors in the Jinjiang River Estuary in Quanzhou, China.
The seasonal and spatial variation in the phytoplankton community structure and the environmental variables were investigated in December (the dry season) 2016 and July (the rainy season) 2017 in the Jinjiang River Estuary, China. We identified a total of 138 species of phytoplankton, which were mainly Chlorophyta, Bacillariophyta, and Cryptophyta in the dry season; however, in the rainy season, only Bacillariophyta were found. In the Jinjiang River Estuary, the species evenness and the biodiversity index were higher in the rainy season and that the species diversity was higher in the dry season. Redundancy analysis (RDA) revealed that the dominant species were statistically related to many of the environmental variables, including the water temperature (WT), pH, salinity (Sal), dissolved oxygen (DO), total phosphorus (TP), and total nitrogen (TN). Among the variables, the Sal, DO, TP, and TN had a significant influence on the dominant species distribution, and the WT and pH also affected the dominant species distribution to some extent.


Intoxication at home due to carbon monoxide production from gas water heaters.
Forensic medicine has a role to play in the community not only when dealing with criminal cases. When the forensic scientist observes fatalities that could have been prevented, he has an obligation to respond with the purpose of preventative measures. In a short period in Copenhagen there were a number of fatalities due to the production of carbon monoxide from gas water heaters. The gas water heaters were in most cases malfunctioning due to sooted convectors and installed without a flue, but at the time of installation maintenance checks were not mandatory, and if carried out they were often unprofessional. It is emphasized that even with well functioning equipment, the danger of intoxication exists when using a heater without a flue over an extended period, if the apartment is thoroughly insulated. The oxygen will then be used in the combustion and CO produced. The symptoms are insidious and uncharacteristic. Examples are described where physicians have failed to diagnose the condition in patients in adjoining apartments. The authorities finally responded to the medical reports with new regulations and with a favourable result. The responsibility with regard to the control of technical installations in a technically advanced society is discussed.


Transcriptional activation in lens epithelial cells following an ocular blunt trauma.
To determine whether an ocular blunt trauma activates anterior ocular segment (cornea and lens) by examining the expression patterns of c-fos and c-jun mRNAs in these tissues of an eye of adult rat following a blunt trauma. Department of Ophthalmology, Wakayama Medical University School of Medicine, Kimiidera, Wakayama, Japan. Adult Wistar rats (n=36) were generally anesthetized by ether inhalation. One eye was hit with an iron sphere (30 gram) that fell to the eye from 1 m. After the procedure, the animals were killed and the affected eye was enucleated at 15, 30, 60, 120, and 180 minutes. In situ hybridization using radiolabeled oligoprobes was used to detect mRNAs of c-fos and c-jun in tissue. The c-fos and c-jun mRNAs were not detected in the epithelium of uninjured cornea and lens by in situ hybridization. The mRNAs for c-fos and c-jun were then detected in corneal epithelium from 15 to 60 minutes posttreatment, and were no longer observed thereafter. In lens epithelium, mRNA for c-fos or c-jun were transiently detected from 15 to 60 minutes or 30 minutes posttreatment, respectively. The c-fos and c-jun mRNAs were transiently expressed in corneal and lens epithelial cells after blunt trauma. Ocular blunt trauma activates corneal and lens epithelial cells without apparent corneal ablation or direct injury in the lens epithelium. Such activation in lens epithelium might be involved in cataractogenesis.


Microvascular endothelial function is impaired in patients with idiopathic hyperaldosteronism.
The aims were to evaluate the relationship between idiopathic hyperaldosteronism (IHA) and grade of vascular function in the macrovasculature and microvasculature. Vascular function, including reactive hyperemia index (RIH), flow-mediated vasodilation (FMD), and nitroglycerine-induced vasodilation (NID) were evaluated in 52 patients with IHA, 53 patients with aldosterone-producing adenoma (APA), and 52 age-, sex-, and blood pressure-matched patients with essential hypertension (EHT). Log RHI was lower in the IHA and APA groups than in the EHT group (0.54 ± 0.25 and 0.55 ± 0.23 versus 0.79 ± 0.28; P < 0.01, respectively). FMD was lower in the APA group than in the EHT group (3.4 ± 2.1% versus 4.8 ± 2.8%; P = 0.02), whereas there was no significant difference in FMD between the IHA and the APA and EHT groups. NID was lower in the APA group than in the EHT group (10.0 ± 4.5% versus 12.5 ± 5.7%; P = 0.03), whereas there was no significant difference in NID between the IHA, APA, and EHT groups. Multiple regression analysis revealed an association of log RHI with plasma aldosterone concentration (t = -2.24; P = 0.03) and an association of FMD with plasma aldosterone concentration (t = -3.07; P < 0.01). Microvascular endothelial function was impaired in patients with IHA compared with that in patients with EHT.