Lack of Increase in Muscle Mitochondrial Protein Synthesis During the Course of Aerobic Exercise and Its Recovery in the Fasting State Irrespective of Obesity.
Acute aerobic exercise induces skeletal muscle mitochondrial gene expression, which in turn can increase muscle mitochondrial protein synthesis. In this regard, the peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), is a master regulator of mitochondrial biogenesis, and thus mitochondrial protein synthesis. However, PGC-1α expression is impaired in muscle of humans with obesity in response to acute aerobic exercise. Therefore, we sought to determine whether muscle mitochondrial protein synthesis is also impaired under the same conditions in humans with obesity. To this end, we measured mitochondrial and mixed-muscle protein synthesis in skeletal muscle of untrained subjects with (body fat: 34.7 ± 2.3%) and without (body fat: 25.3 ± 3.3%) obesity in a basal period and during a continuous period that included a 45 min cycling exercise (performed at an intensity corresponding to 65% of heart rate reserve) and a 3-h post-exercise recovery. Exercise increased PGC-1α mRNA expression in muscle of subjects without obesity, but not in subjects with obesity. However, muscle mitochondrial protein synthesis did not increase in either subject group. Similarly, mixed-muscle protein synthesis did not increase in either group. Concentrations of plasma amino acids decreased post-exercise in the subjects without obesity, but not in the subjects with obesity. We conclude that neither mitochondrial nor mixed-muscle protein synthesis increase in muscle of humans during the course of a session of aerobic exercise and its recovery period in the fasting state irrespective of obesity. Trial Registration: The study has been registered within ClinicalTrials.gov (NCT01824173).


Food, Health, and Mitigation of Climate change in Italy
to provide evidence on how diet can influence health, greenhouse gas (GHG) emissions, and land use. cohort study. data collected in the EPIC Italy cohort (N. 47,749). hazard ratios (HR) for overall mortality and for cancer incidence in association with a sustainable diet (EAT-Lancet). sustainable diets are characterized by lower associated GHG emissions and lower land use (LU). Adherence to the guidelines proposed by the EAT-Lancet Commission was considered. This diet was associated with lower HRs for mortality and cancer incidence in EPIC Italy, estimated with Cox models accounting for potential confounders and stratified by sex. The hazard ratios for overall mortality showed a dose-response relationship with quartiles of diets associated with high GHG emissions, land use, and high distance from the EAT-Lancet diet calculated using a novel index, the EAT-Lancet distance index (EatDI). The HR for overall cancer incidence was also higher in the population with non-sustainable diets. the association among dietary GHG emissions, LU, and EatDI and overall mortality and overall cancer incidence suggests that promoting diets with low associated environmental impact can be an effective mitigation strategy with important co-benefits.


[The results of longitudinal use of copaxone and betaferon in Moscow Multiple Sclerosis Center: issues of efficacy and adherence to therapy].
In last decades, practical neurologists are able to use DMT in multiple sclerosis (MS) in every day practice. This paper presents data of 3-year study of DMT (copaxone and betaferon) treatment of 280 patients with definite diagnosis of multiple sclerosis (MS), 166 patients regularly receiving DMT (104--copaxone and 62--betaferon) for, at least, 3 years. Clinical symptoms of the patients, reasons of treatment withdrawal (48--copaxone and 31--betaferon) and the features of MS course after the withdrawal are analyzed. Patients who received betaferon previously had more severe MS course with frequent relapses, half of them had secondary progressive MS course (SPMS) with relapses. This made impossible a direct comparison of the data of two treatment groups. Treatment with copaxone reduced 5 times annual relapse rate, from 1.45 before DMT to 0.27 during these 3 years (p < 0.001), and this reduction remained stable. For 36 months, 40.4% of patients were relapse-free though all of them had, at least, one relapse per year before the treatment. No EDSS progression was observed in 80% of these patients. Treatment with betaferon caused the reduction of relapse rate from 1,84 to 0,69 per year (2.7 times), 8 patients (26%) with previously active RMS being relapse-free for 36 months. In 31 patients with SPMS, the reduction of relapse rate was also significant, from 1.89 to 0.49 (3.8 times, p < 0.001). Twenty-two patients (71%) with previous SPMS did not have EDSS progression for 36 months that indicate the positive effect of the therapy. Side-effects were moderate and were not the main cause of the treatment withdrawal. The latter was caused mainly by clinical un efficacy, most frequently by the increase of EDSS due to transformation of the MS course to SPMS without relapses and poor understanding by the patient of the goals and the possibilities of DMT. These facts stress the significance of improving compliance, motivation and adherence to DMT in everyday neurological practice.


Association of the -344T/C polymorphism in aldosterone synthase gene promoter with left ventricular structure in Chinese Han: A meta-analysis.
No consensus view has been published on the relationship between the aldosterone synthase gene (CYP11B2) -344C/T polymorphism and left ventricular hypertrophy (LVH) in Chinese Han. We undertook a meta-analysis to investigate the potential association of this polymorphism and left ventricular structure-related phenotypes, including left ventricular mass (LVM), left ventricular mass index (LVMI), left ventricular end systolic diameter (LVESD), left ventricular end diastolic dimension (LVEDD), left ventricular posterior wall thickness (LVPWT), and interventricular septal wall thickness (IVS). Studies in English and Chinese were found based on a systematic search of Medline, Embase, CNKI, and Wanfang databases. The dominant model (TT vs. TC+CC) and homozygote model (TT vs. CC) were selected to examine the association between the -344C/T polymorphism and LVH. The random-effects model was used to pool data. From a total of 3104 participants, despite the investigation of six echocardiographic indicators, we found no significant association between the -344C/T variant and LVH in the whole group and the subgroup analyses by blood pressure. However, in the subgroup of northern Han Chinese, TT genotype had higher LVPWT than CC genotype and TC genotype (pheterogeneity = 0.4, pvalue = 0.04, 95% CI 0.09 (0.00, 0.18)). In addition, no evidence of publication bias was observed. In conclusion, our meta-analysis indicated that subjects with TT genotype might have higher risk of developing LVH in northern Han Chinese.


Fear and anxiety in children and adolescents.
The author reviews fears and anxiety in children and adolescents. In particular, the nature and prevalence of fears and anxiety disorders, including panic disorder, are described. This is followed by a description of comorbidity and gender differences, and the stability or chronicity of these disorders. Factors believed to contribute to the development of childhood fear and anxiety are outlined, and finally the treatments for these disorders are reviewed.


Ultrastructural changes in rat colon following 1,2-dimethylhydrazine-induced colon carcinogenesis: protection by zinc.
The present study evaluated the modulatory effects of zinc on 1,2-dimethylhydrazine (DMH)-induced ultrastructural changes in rat colon as well as on [(3)H]thymidine uptake and [(14)C]D-glucose metabolism. The rats were segregated into four groups: normal control, DMH treated, zinc treated, DMH + zinc treated. Initiation and induction of colon carcinogenesis was achieved through weekly subcutaneous injections of DMH (30 mg/kg body weight) for 8 and 16 weeks, respectively. Zinc was supplemented to rats at a dose level of 227 mg/L in drinking water, ad libitum for two different time durations of 8 and 16 weeks. The study revealed a significant decrease in zinc concentration in serum and colon following DMH treatment to rats, which upon zinc supplementation were recovered to near normal levels. A significant increase in in vitro [(3)H]thymidine uptake was observed following 16 weeks of DMH treatment. Further, a significant increase in the [(14)C]glucose turnover was observed following 8 and 16 weeks of DMH treatment. Simultaneous supplementation of zinc to DMH-treated rats for 16 weeks significantly decreased the uptake of [(3)H]thymidine and [(4)C]glucose when compared to DMH alone-treated rats. Changes in the ultrastructural architecture of colonic cells were evident following both treatment schedules of DMH; however, the changes were more distinguishable following 16 weeks of DMH treatment. The most obvious changes were seen in nuclear shape and disruption of cellular integrity, which upon zinc supplementation was appreciably improved. In conclusion, the study suggests positive beneficial effect of zinc against chemically induced colonic preneoplastic progression in rats.


How to understand divergent views on bipolar disorder in youth.
There are two divergent viewpoints on the phenomenology and outcome of bipolar I (BP I) disorder in youth. Disparities evolved as unintended consequences from investigators' inconsistencies both in translating the Diagnostic and Statistical Manual of Mental Disorders (DSM)-III, DSM-III-R, and DSM-IV criteria and in operationalizing them differently in their standardized assessments. Rates of conservatively diagnosed BP I are lower both in community studies of youths than in adults and from liberally defined BP I in youths. Rates of co-occurring attention-deficit hyperactivity disorder (ADHD) are lower in conservatively than liberally defined children and adolescents with BP I. Rates of both BP I and of ADHD are lower in offspring of BP I probands, and outcome more closely approximates that of adults with BP I in conservatively versus liberally defined children and teens with BP I. Both perspectives can claim evidence for reliability and validity that support their positions. However, the samples are so different that it is difficult to compare studies conducted from these different perspectives.


Progression of an osteoid osteoma to an osteoblastoma. Case report.
The authors report the unusual case of a 25-year-old man with occipitocervical pain related to a lesion of the C-1 lateral mass. Initially this lesion measured 8 mm and exhibited radiological features of an osteoid osteoma. Seven years later, as pain increased and became unresponsive to antiinflammatory drugs, computerized tomography scanning demonstrated progression to a 16-mm lesion, highly suspicious of an osteoblastoma. After mobilization of the vertebral artery from the C-1 groove, the lesion was completely resected via an anterolateral approach. Complete symptomatic relief, restoration of cervical range of motion and preservation of cervical stability were achieved immediately after surgery, and the results were confirmed at the 4-year follow-up examination. Pathological examination of tissue samples confirmed the diagnosis of osteoblastoma. Osteoid osteoma rarely evolves to osteoblastoma. Deterioration of a patient's ability to control pain is a warning sign. Insight into such cases underlines the importance of close long-term radiological follow-up examination in patients with conservatively treated osteoid osteomas.


Change in pharmacokinetic behavior of intravenously administered midazolam due to increased CYP3A2 expression in rats treated with menthol.
Menthol is used widely as a constituent of functional foods and chemical drugs. The present study investigated changes in the pharmacokinetic behavior of intravenously administered midazolam (MDZ), a probe for CYP3A, when rats were treated with menthol. The study also examined which isoforms of CYP3A1 and 3A2 were menthol-inducible and contributed to the altered disposition of midazolam. Menthol was administered intraperitoneally to rats once daily for 3 days at a dose of 10 mg/kg, while the control rats received vehicle alone. The pharmacokinetic examination of i.v. administered midazolam revealed that serum midazolam concentrations at each sampling point were lower in the menthol-treated rats than in the control rats. Regarding the pharmacokinetic parameters of the menthol-treated group, the area under the curve (AUC) was decreased significantly and, correspondingly, the elimination rate constant at terminal phase (ke) was increased significantly without significant changes in the volume of distribution at steady state (Vdss). The metabolic production of the 1'-hydroxylated and 4'-hydroxylated forms of MDZ by hepatic microsomes was significantly greater in the menthol-treated rats than in the control rats. The expression levels of mRNA and protein for hepatic CYP3A2 were more than 2.5-fold higher than the control levels when the rats were treated with menthol, whereas no changes were observed in the expression levels of CYP3A1. These results indicate that menthol enhanced the elimination clearance of midazolam by inducing hepatic CYP3A2 and that careful attention should be paid when menthol is ingested in combination with drugs that act as substrates for CYP3A.


Mass transfer from the rotor to the stator for improving the speed of the piezoelectric motor based on centrifugal force.
To improve the speed of a piezoelectric motor based on centrifugal force, a method is proposed on the basis of mass transfer from the rotor to the stator. Multi-degree-of-freedom vibration models are established before and after mass transfer. A mass of 150 g is transferred from the six-hole rotor to the stator. This process increases the rotation frequency of the rotor under the same friction loss and increases the energy fed into the rotor by the stator. The motor operates at a frequency close to the resonance frequency. The change in the initial phase with the operating frequency close to the resonance frequency is analyzed, and the phase adjustment device and the signal processing circuit are designed. Two prototypes, one with and one without mass transfer, are fabricated and measured. As the initial phase is adjusted from 0° to 75°, the motor rotation frequency gradually increases, approaching the resonant frequency of the motor. When the excitation voltage is 790 Vp-p, the speed of the piezoelectric motor with a mass transfer of 150 g reaches 11 004 rpm, which is 89% faster than the speed of that without mass transfer.


The avermectins: A new family of antiparasitic agents.
The avermectins are macrocyclic lactones produced by fermentation of the soil micro-organism Streptomyces avermitilis. They show activity against a broad range of nematodes and arthropod parasites of domestic animals at dose rates of 300 microgram/kg or less. Unlike the macrolide or polyene antibiotics, they lack significant antibacterial or antifungal activity. By oral or parenteral administration, avermectins are active against gastrointestinal nematodes and lungworms, and important ectoparasites such as lice, mange mites, ticks and larval stages of flies. They show excellent activity against parasites resistant to existing anthelmintics or ectoparasiticides. The avermectins appear to cause paralysis of nematodes and arthropods by opening gamma-aminobutyric acid-mediated chloride channels at the neuromuscular junction.


Racial disparity in survival among patients with advanced/recurrent endometrial adenocarcinoma: a Gynecologic Oncology Group study.
Previous studies have reported shorter survival of black women compared with white women who had advanced/recurrent endometrial cancer. It has been suggested that this may reflect racially based differences in treatment. The authors retrospectively reviewed data from 169 black women and 982 white women with International Federation of Gynecologic Oncology (FIGO) Stage III, Stage IV, or recurrent endometrial carcinoma who were participants in 1 of 4 Gynecologic Oncology Group randomized treatment trials of doxorubicin alone or combined with paclitaxel and/or cisplatin. Demographic, histologic, treatment, and outcome data were analyzed to estimate survival, and between-group comparisons were performed. The pooled data revealed that black women were more likely to have papillary serous histology (P < .001), Stage IV disease (P < .001), and higher tumor grade (P < .001) compared with white women, and survival was worse among black women than among white women (median survival, 10.6 months vs. 12.2 months, respectively; P < .001). A Cox proportional hazards regression analysis that was adjusted for performance status, disease stage, tumor histology, tumor grade, and treatment demonstrated worse survival for black women (hazards ratio, 1.26, 95% confidence interval, 1.06-1.51; P = .010). The data from a large group of women with advanced/recurrent endometrial cancer suggested that a racial disparity in survival persists, despite the finding that black women and white women received similar treatment. Although the causes of racial disparity in endometrial cancer remain to be elucidated, socioeconomic, biologic, and cultural factors should be investigated to identify the etiologic origins of this multifactorial healthcare problem.


[Cholecystectomy in the laparoscopic era].
Since 1991 laparoscopic cholecystectomy has been performed on 323 patients; 47 patients underwent conversion to open surgery. In the same period, 46 patients were primarily selected for open cholecystectomy. Half the patients were operated on because of gallbladder colic (the sole symptom). Conversion to open operation (14%) occurred not so much because of peroperative complications, but rather because of anatomical problems. On the fourth postoperative day, one patient died of septicaemia caused by iatrogenic diathermy damage to the duodenum. One patient developed a stricture of the choledochus as a result of ischemia. This was caused by dissecting the choledochus, having mistaken it for the ductus cysticus which was missing in this anatomic variant.


Tetramethylpyrazine prevents contrast-induced nephropathy by inhibiting p38 MAPK and FoxO1 signaling pathways.
Apoptosis is recognized as an important mechanism in contrast-induced nephropathy (CIN). As tetramethylpyrazine (TMP) has been recently found to be renoprotective and anti-apoptotic in multiple kidney injuries, we hypothesized that TMP would prevent CIN. An experimental model of CIN was established in rats. Serum creatinine, blood urea nitrogen, plasma cystatin C, urinary N-acetyl-β-glucosaminidase, and urinary γ-glutamyl transpeptidase were measured to evaluate kidney function. Apoptosis was assessed by transmission electron microscopy, transferase-mediated deoxyuridine triphosphate nick end-labeling staining, and poly-ADP-ribose polymerase cleavage. Fork-head box O1 transcriptional factor (FoxO1) mRNA expression was evaluated by quantitative real-time PCR. Phospho-p38 mitogen-activated protein kinase (MAPK) protein expression was assessed by immunohistochemistry and Western blotting. TMP significantly attenuated the resulting renal dysfunction and renal tubular cell apo-ptosis. Mechanistically, TMP decreased the expression of phospho-p38 MAPK protein and attenuated the increased FoxO1 mRNA and nuclear protein expression. In addition, TMP inhibited inducible nitric oxide synthase and Bax protein expression while it upregulated Bcl-2. In summary, this study demonstrated the protective role of TMP against CIN and indicated the effects of TMP may be mediated by the inhibition of p38 MAPK and FoxO1 pathways. Thus, TMP may be a new potential therapeutic agent to prevent CIN.


Distinct NKT cell subsets are induced by different Chlamydia species leading to differential adaptive immunity and host resistance to the infections.
We investigated the role of NKT cells in immunity to Chlamydia pneumoniae and Chlamydia muridarum infections using a combination of knockout mice and specific cellular activation approaches. The NKT-deficient mice showed exacerbated susceptibility to C. pneumoniae infection, but more resistance to C. muridarum infection. Activation of NKT reduced C. pneumoniae in vivo growth, but enhanced C. muridarum infection. Cellular analysis of invariant NKT cells revealed distinct cytokine patterns following C. pneumoniae and C. muridarum infections, i.e., predominant IFN-gamma in the former, while predominant IL-4 in the latter. The cytokine patterns of CD4(+) and CD8(+) T cells matched those of NKT cells. Our data provide in vivo evidence for a functionally diverse role of NKT cells in immune response to two intracellular bacterial pathogens. These results suggest that distinct NKT subsets are induced by even biologically closely related pathogens, thus leading to differential adaptive immune response and infection outcomes.


Pre-Clinical Proof of Concept: Intra-Carotid Injection of Autologous CD34-Positive Cells for Chronic Ischemic Stroke.
This study was conducted to evaluate the safety and efficacy of human peripheral blood CD34 positive (CD34+) cells transplanted into a murine chronic stroke model to obtain pre-clinical proof of concept, prior to clinical testing. Granulocyte colony stimulating factor (G-CSF) mobilized human CD34+ cells [1 × 104 cells in 50 μl phosphate-buffered saline (PBS)] were intravenously (iv) or intra-carotid arterially (ia) transplanted 4 weeks after the induction of stroke (chronic stage), and neurological function was evaluated. In this study, severe combined immune deficiency (SCID) mice were used to prevent excessive immune response after cell therapy. Two weeks post cell therapy, the ia CD34+ cells group demonstrated a significant improvement in neurological functions compared to the PBS control. The therapeutic effect was maintained 8 weeks after the treatment. Even after a single administration, ia transplantation of CD34+ cells had a significant therapeutic effect on chronic stroke. Based on the result of this pre-clinical proof of concept study, a future clinical trial of autologous peripheral blood CD34+ cells administration in the intra-carotid artery for chronic stroke patients is planned.


Giant cell angiofibroma of the orbit with periosteal adherence.
We report a case of orbital giant cell angiofibroma, an unusual, recently reported benign spindle cell neoplasm. Preoperative clinical assessment and radiology suggested a benign mass and early operative findings were in concordance with this. Surgical excision was however, hampered by periosteal adhesion and lack of distinct encapsulation in the posterior part of the lesion. The histology of giant cell angiofibroma and its principle pathological differential diagnoses is discussed. As with some lymphangiomas, this is another benign orbital tumour which may present difficulties in complete surgical excision that are not anticipated based on the preoperative findings.


Fz2 and cdc42 mediate melanization and actin polymerization but are dispensable for Plasmodium killing in the mosquito midgut.
The midgut epithelium of the mosquito malaria vector Anopheles is a hostile environment for Plasmodium, with most parasites succumbing to host defenses. This study addresses morphological and ultrastructural features associated with Plasmodium berghei ookinete invasion in Anopheles gambiae midguts to define the sites and possible mechanisms of parasite killing. We show by transmission electron microscopy and immunofluorescence that the majority of ookinetes are killed in the extracellular space. Dead or dying ookinetes are surrounded by a polymerized actin zone formed within the basal cytoplasm of adjacent host epithelial cells. In refractory strain mosquitoes, we found that formation of this zone is strongly linked to prophenoloxidase activation leading to melanization. Furthermore, we identify two factors controlling both phenomena: the transmembrane receptor frizzled-2 and the guanosine triphosphate-binding protein cell division cycle 42. However, the disruption of actin polymerization and melanization by double-stranded RNA inhibition did not affect ookinete survival. Our results separate the mechanisms of parasite killing from subsequent reactions manifested by actin polymerization and prophenoloxidase activation in the A. gambiae-P. berghei model. These latter processes are reminiscent of wound healing in other organisms, and we propose that they represent a form of wound-healing response directed towards a moribund ookinete, which is perceived as damaged tissue.


Cognitive impairment is associated with Hoehn and Yahr stages in early, de novo Parkinson disease patients.
The relationship between motor impairment and cognitive deterioration has long been described in Parkinson's disease (PD). The aim of the study was to compare cognitive performance of de novo PD patients in relation to the motor impairment severity according to Hoehn and Yahr (HY) stages. Forty de novo PD patients at HY stage I and 40 patients at HY stage II completed a standardized neuropsychological battery. A multivariate analysis of covariance was used to compare cognitive performance between HY groups. Odds ratios (ORs) were employed to explore the risk of cognitive impairment between HY stages. Finally, the prevalence of mild cognitive impairment (MCI) was estimated for patients in HY stage I and II. Patients at HY stage I obtained better scores on neuropsychological tests than patients at HY stage II (p = 0.001). Univariate analysis of covariance revealed significant differences between HY stages on Rey's auditory verbal learning test -immediate recall (p < 0.0001), 10 points Clock Drawing Test (p = 0.002), and Rey-Osterrieth Complex Figure Test -copy (p < 0.0001). ORs of having cognitive impairment were greater for HY stage II than stage I group. MCI occurred in 7.5% of patients in HY stage I, and in 42.5% of patients in HY stage II. In de novo PD patients, the severity of motor impairment at the diagnosis is associated to cognitive deficits and higher risk of MCI.


Front-line chemotherapy with docetaxel and gemcitabine administered every two weeks in patients with metastatic breast cancer: a multicenter phase II study.
To evaluate the docetaxel-gemcitabine combination administered every 2 weeks in women with untreated metastatic breast cancer (MBC). Fifty-two patients with MBC received docetaxel 65 mg/m2 as front-line chemotherapy intravenously over 1 h followed by gemcitabine 1,500 mg/m2 intravenously over 30 min on days 1 and 14. Cycles were repeated every 28 days without prophylactic growth factor support. Twenty-eight (54%) patients had previously received chemotherapy as adjuvant or neoadjuvant treatment. Thirty-six (69%) patients had visceral disease including 20 (38%) with liver metastases. All patients were evaluated for toxicity and 45 for response. In an intention-to-treat analysis, a complete response occurred in 7 (13%) patients and partial response in 24 (46%) for an overall response rate of 59% (95% CI: 46.3-73.0%). The response rate was 68% for the 28 patients who had previously received adjuvant or neoadjuvant chemotherapy and 67% for the 36 patients with visceral metastases. The median duration of response was 6.1 months and the median time to disease progression 10.9 months. A total of 254 cycles were administered with dose reduction in 26 (10%) cycles and no lethal toxicity. Grade III-IV neutropenia occurred in 17 (33%) patients and thrombocytopenia in 3 (6%). Febrile neutropenia developed in 3 (6%) patients. Nonhematological toxicity was generally mild. The docetaxel-gemcitabine combination is an active and well-tolerated front-line treatment for patients with MBC. This regimen represents a suitable option especially for women relapsing after anthracycline-based adjuvant chemotherapy.


[Ritual circumcision : a society challenge].
Male circumcision is one of the most common surgical procedure in the world. At the world level, 30 % of the men are circumcised. The reasons of circumcisions are ritual for 97 %. The medical circumcisions represent less than 3 %. The non-medical circumcision made in the childhood became, these last years, a highly polemical subject entailing deep passionate debates within our societies both on the political and medical point. Our society is in constant changes with the apparition of an undeniable multiculturalism because of the immigrations. The requests of ritual circumcisions are a reality. As specialists of the child or as family doctors, we have to answer it in a professional way by respecting the child and his family, the swiss legislation and the medical ethics.


Psychometric properties of End Stage Renal Disease-Adherence Questionnaire-Sinhalese version among patients receiving haemodialysis.
The chronic kidney disease is a leading public health concern, particularly in low-to middle-income countries, while the number of patients receiving haemodialysis is rapidly increasing. Adherence to a complex treatment regimen is vital for those patients on maintenance haemodialysis though the precise evaluation is reported inadequately. This study aimed to evaluate the psychometric properties of Sinhalese version of End Stage Renal Disease-Adherence Questionnaire (SINESRD-AQ) to assess treatment adherence behaviour among patients receiving haemodialysis in a Sri Lankan hospital. The cultural adaptation of ESRD-AQ involved forward and back translation, expert committee consolidation and pretesting among patients (n = 10). Face and content validity of the questionnaire was evaluated using a modified Delphi technique. Construct validity of the subscales of SINESRD-AQ was evaluated using confirmatory factor analysis (CFA). A descriptive cross-sectional study among a consecutive sample of 150 patients receiving haemodialysis in a selected Teaching hospital, Sri Lanka was involved in performing CFA. Reliability was confirmed with test-retest reliability. Excellent face and content validity were reported with Item level content validity index (0.83-1.0), Average Item level content validity index for whole scale (0.93), Item level content validity ratio (0.67-1.0) and modified kappa statistic coefficient (0.81-1.0). CFA of two subscales demonstrated better indices closure to the model fit with five- item two factor model for direct adherence behaviour subscale and eight-item two factor model for attitude/perception subscale. The intra class correlation coefficient of 0.837 (p<0.001) and 0.752 (p<0.001) indicated acceptable test-retest reliability of direct adherence behaviour and attitude/perception subscale respectively. The study confirmed SINESRD-AQ as a valid and reliable measure which enables periodic assessment of treatment adherence behaviour of the patients receiving haemodialysis in a Sri Lankan hospital.


Metabolism of constituents in Huangqin-Tang, a prescription in traditional Chinese medicine, by human intestinal flora.
In the course of studies on the metabolism of active components of Huangqin-Tang by human intestinal flora (HIF), Huangqin-Tang and all individual herbs in the decoctions were incubated with a human fecal suspension separately. By using a high-performance liquid chromatographic (HPLC) method which was previously established in our laboratory, the metabolites in both the compound prescription and all the single herb decoctions were identified and determined both qualitatively and quantitatively. We found that the constituents of Huangqin-Tang, incluing baicalin (baicalein 7-glucuronide; BG), wogonoside (wogoninoglucuronide; WG), oroxylin-A-glucuronide (OG) from Scutellariae Radix, paeoniflorin (PF) from Paeoniae Radix, liquiritin (liquiritigenin 4'-O-glucoside; LG), isoliquirtin (isoliquiritigenin 4-glucoside; ILG) and glycyrrhizic acid (GL) from Glycyhhizea Radix, were converted to their metabolites baicalein (B), wogonin (W), oroxylin-A (O), paeonimetabolin-I (PM-I), liquiritigenin (L), isoliquiritigenin (IL) and glycyrrhetinic acid (GA) by HIF. The contents of the metabolites in Huangqin-Tang and in each single herb decoction increased significantly after incubation with intestinal flora. Comparing with single herb decoctions, the transformation of BG, WG, OG, LG and ILG in the compound prescription was promoted, however, that of PF and GL was inhibited. All the results suggested that the glycosides of many medicinal herbs could be converted to aglycones by HIF, and the metabolism of most glycosides was improved in the compound prescription.


Magnetic resonance imaging of the brachial plexus in patients with multifocal motor neuropathy.
We studied whether magnetic resonance (MR) imaging of the brachial plexus is useful to distinguish multifocal motor neuropathy (MMN) from lower motor neuron disease (LMND) and whether abnormalities resemble those of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). We compared MR images of the brachial plexus of nine patients with MMN with scans from five patients with CIDP, eight patients with LMND, and 174 controls. In two patients with MMN, and in three patients with CIDP, the MR images showed an increased signal intensity on the T2-weighted images of the brachial plexus. Two other patients with MMN demonstrated a more focal, increased signal intensity on the T2-weighted images, occurring in one patient only in the axilla, and in the other patient in the axilla and in the ventral rami of the roots. MR images of the brachial plexus of eight patients with LMND were normal. The distribution of the MR imaging abnormalities corresponded with the distribution of symptoms of the patients: asymmetrical in MMN and symmetrical in CIDP. These findings demonstrate that MR imaging abnormalities of the brachial plexus in patients with MMN resemble those seen in CIDP and may be useful to distinguish MMN from LMND.


The variant of post-Newtonian mechanics with generalized fractional derivatives.
In this article, we investigate mathematically the variant of post-Newtonian mechanics using generalized fractional derivatives. The relativistic-covariant generalization of the classical equations for gravitational field is studied. The equations (i) match the weak Newtonian limit on the moderate scales and (ii) deliver a potential higher than Newtonian on certain large-distance characteristic scales. The perturbation of the gravitational field results in the tiny secular perihelion shift and exhibits some unusual effects on large scales. The general representation of the solution for the fractional wave equation is given in the form of retarded potentials. The solutions for the Riesz wave equation and classical wave equation are clearly distinctive in an important sense. The hypothetical gravitational Riesz wave demonstrates the space diffusion of the wave at the scales of metric constant. The diffusion leads to the blur of the peak and disruption of the sharp wave front. This contrasts with the solution of the D'Alembert classical wave equation, which obeys the Huygens principle and does not diffuse.


Introduction of a novel service model to improve uptake and adherence with cardiac rehabilitation within Buckinghamshire Healthcare NHS Trust.
Buckinghamshire Healthcare NHS Trust (BHT) carried out a cardiac rehabilitation (CR) service redesign aimed at optimising patient recruitment and retention and decreasing readmissions. A single centre observational study and local service evaluation were carried out to describe the impact of the novel technology-enabled CR model. Data were collected for adult patients referred for CR at BHT, retrospectively for patients referred during the 12-month pre-implementation period (Cohort 1) and prospectively for patients referred during the 12-month post-implementation period (Cohort 2). The observational study included 350 patients in each cohort, seasonally matched; the service evaluation included all eligible patients. No data imputation was performed. In the observational study, a higher proportion of referred patients entered CR in Cohort 2 (84.3%) than Cohort 1 (76.0%, P = 0.006). Fewer patients in Cohort 2 had ≥1 cardiac-related emergency readmission within 6 months of discharge (4.3%) than Cohort 1 (8.9%, P = 0.015); readmissions within 30 days and 12 months were not significantly different. Median time to CR entry from discharge was significantly shorter in Cohort 2 (35.0 days) than Cohort 1 (46.0 days, P < 0.001). The CR completion rate was significantly higher in Cohort 2 (75.6%) than Cohort 1 (47.4%, P < 0.001); median CR duration for completing patients was significantly longer in Cohort 2 (80.0 days) than Cohort 1 (49.0 days, P < 0.001). Overall, similar results were observed in the service evaluation. Introduction of the novel technology-enabled CR model was associated with short-term improvements in emergency readmissions and sustained increases in CR entry, duration and completion.


Myocardial Dysfunction and Shock after Cardiac Arrest.
Postarrest myocardial dysfunction includes the development of low cardiac output or ventricular systolic or diastolic dysfunction after cardiac arrest. Impaired left ventricular systolic function is reported in nearly two-thirds of patients resuscitated after cardiac arrest. Hypotension and shock requiring vasopressor support are similarly common after cardiac arrest. Whereas shock requiring vasopressor support is consistently associated with an adverse outcome after cardiac arrest, the association between myocardial dysfunction and outcomes is less clear. Myocardial dysfunction and shock after cardiac arrest develop as the result of preexisting cardiac pathology with multiple superimposed insults from resuscitation. The pathophysiology involves cardiovascular ischemia/reperfusion injury and cardiovascular toxicity from excessive levels of inflammatory cytokine activation and catecholamines, among other contributing factors. Similar mechanisms occur in myocardial dysfunction after cardiopulmonary bypass, in sepsis, and in stress-induced cardiomyopathy. Hemodynamic stabilization after resuscitation from cardiac arrest involves restoration of preload, vasopressors to support arterial pressure, and inotropic support if needed to reverse the effects of myocardial dysfunction and improve systemic perfusion. Further research is needed to define the role of postarrest myocardial dysfunction on cardiac arrest outcomes and identify therapeutic strategies.


Effects of a Contextual Adaptation of the Unified Protocol in Multiple Emotional Disorders in Individuals Exposed to Armed Conflict in Colombia: A Randomized Clinical Trial.
A transdiagnostic treatment, the Unified Protocol, is as effective as single diagnostic protocols in comorbid emotional disorders in clinical populations. However, its effects on posttraumatic stress disorder and other emotional disorders in individuals living in war and armed conflict contexts have not been studied. To evaluate the efficacy of a cultural and contextual adaptation of the Unified Protocol (CXA-UP) on posttraumatic stress disorder, anxiety, and depression compared to waitlist control in individuals exposed to armed conflict in Colombia. From April 2017 to March 2020, 200 participants 18 years and older were randomly assigned to the CXA-UP or to a waitlist condition. CXA-UP consisted of 12 to 14 twice-a-week or weekly individual 90-minute face-to-face sessions. Outcomes were assessed at baseline, posttreatment, and 3 months following treatment. Analyses were performed and compared for all randomly allocated participants (intent-to-treat [ITT]) and for participants who completed all sessions and posttreatment measures (per protocol [PP]). The study took place at an outpatient university center and included individuals who were registered in the Colombian Victims Unit meeting DSM-5 diagnostic criteria for posttraumatic stress disorder, anxiety, or depression or were severely impaired by anxiety or depression. Individuals who were receiving psychological therapy, were dependent on alcohol or drugs, were actively suicidal or had attempted suicide in the previous 2 months, had psychosis or bipolar disorder, or were cognitively impaired were excluded. CXA-UP or waitlist. Primary outcomes were changes in anxiety, depression, and somatic scores on the Patient Health Questionnaire and Posttraumatic Stress Disorder Checklist for DSM-5. Among the 200 participants (160 women [80.0%]; 40 men [20.0%]; mean [SD] age, 43.1 [11.9] years), 120 were randomized to treatment and 80 to waitlist. Results for primary outcomes in the ITT analysis showed a significant pretreatment-to-posttreatment reduction when comparing treatment and waitlist on the posttraumatic stress disorder checklist for DSM-5 scores (slope [SE], -31.12 [3.00]; P < .001; Cohen d, 0.90; 90% CI, 0.63-1.19), 9-item Patient Health Questionnaire (PHQ-9) (slope [SE],-11.94 [1.30]; P < .001; Cohen d, 0.77; 90% CI, 0.52-1.06), PHQ-anxiety (slope [SE], -6.52 [0.67]; P < .001; Cohen d, 0.82; 90% CI, 0.49-1.15), and PHQ-somatic (slope [SE], -8.31 [0.92]; P < .001; Cohen d, 0.75; 90% CI, 0.47-1.04). In this study, significant reductions and large effect sizes in all measures of different emotional disorders showed efficacy of a single transdiagnostic intervention in individuals exposed to armed conflicts. ClinicalTrials.gov Identifier: NCT03127982.


On Addiction, Complexity, and Freedom: Toward a Liberation-Focused Addiction Treatment.
This article outlines a liberation-focused model of addiction treatment. Drawing on the Latin root word "addictus", addiction is seen as slavery and freedom, rather than the cessation of drug and alcohol use, is proposed as a viable, alternative treatment goal. Freedom is defined as: (1) the capacity to create a life of social and internal complexity and multiplicity; (2) the ability to make choices from an array of options; and (3) the possibility of engaging in long-term, goal-directed behavior. This vision of personal liberation is then embedded within a biopsychosocial model of care and treatment. Examples of how biomedical, psychological, and social interventions can each serve to promote the goal and experience of freedom and liberation are provided. Engaging in identity projects and using harm reduction interventions and philosophies are also seen as key to this transformative journey.


Protocol for Local On-Site Dialysate Production for Continuous Renal Replacement Therapy during the COVID-19 Pandemic.
AKI frequently occurs in patients with COVID-19, and kidney injury severe enough to require RRT is a common complication among patients who are critically ill. During the surge of the pandemic, there was a high demand for dialysate for continuous RRT, and this increase in demand, coupled with vulnerabilities in the supply chain, necessitated alternative approaches, including internal production of dialysate. Using a standard hemodialysis machine and off-the-shelf supplies, as per Food and Drug Administration guidelines, we developed a method for on-site dialysate production that is adaptable and can be used to fill multiple bags at once. The use of a central reverse osmosis unit, dedicated hemodialysis machine, sterile bags with separate ports for fill and use, and frequent testing will ensure stability, sterility, and-therefore-safety of the produced dialysate. The dialysate made in house was tested and it showed both stability and sterility for at least 30 hours. This detailed description of our process for generating dialysate can serve as a guide for other programs experiencing similar vulnerabilities in the demand versus supply of dialysate.


Changes in the stability and biomechanics of P22 bacteriophage capsid during maturation.
The capsid of P22 bacteriophage undergoes a series of structural transitions during maturation that guide it from spherical to icosahedral morphology. The transitions include the release of scaffold proteins and capsid expansion. Although P22 maturation has been investigated for decades, a unified model that incorporates thermodynamic and biophysical analyses is not available. A general and specific model of icosahedral capsid maturation is of significant interest to theoreticians searching for fundamental principles as well as virologists and material scientists seeking to alter maturation to their advantage. To address this challenge, we have combined the results from orthogonal biophysical techniques including differential scanning fluorimetry, atomic force microscopy, circular dichroism, and hydrogen-deuterium exchange mass spectrometry. By integrating these results from single particle and population measurements, an energy landscape of P22 maturation from procapsid through expanded shell to wiffle ball emerged, highlighting the role of metastable structures and the thermodynamics guiding maturation. The propagation of weak quaternary interactions across symmetric elements of the capsid is a key component for stability in P22. A surprising finding is that the progression to wiffle ball, which lacks pentamers, shows that chemical and thermal stability can be uncoupled from mechanical rigidity, elegantly demonstrating the complexity inherent in capsid protein interactions and the emergent properties that can arise from icosahedral symmetry. On a broader scale, this work demonstrates the power of applying orthogonal biophysical techniques to elucidate assembly mechanisms for supramolecular complexes and provides a framework within which other viral systems can be compared.


Inefficient enhancement of viral infectivity and CD4 downregulation by human immunodeficiency virus type 1 Nef from Japanese long-term nonprogressors.
It has been reported that patients infected with nef-defective human immunodeficiency virus type 1 (HIV-1) do not progress to AIDS; however, mutations that abrogate Nef expression are not common in long-term nonprogressors (LTNPs). We postulated that Nef function might be impaired in LTNPs, irrespective of the presence or absence of detectable amino acid sequence anomalies. To challenge this hypothesis we compared in vitro function of nef alleles that were derived from three groups of Japanese patients: LTNPs, progressors, and asymptomatic carriers (ACs). The patient-derived nef alleles were subcloned into a nef-defective infectious HIV-1 molecular clone and an expression vector. We first examined Nef-dependent enhancement of infection in a single-round infectivity assay by the use of MAGNEF cells, in which Nef is required more strictly for the infection than in the parent MAGI cells. All nef alleles from LTNPs showed reduced enhancement in the infectivity of nef-defective HIV-1 mutants compared to the nef alleles of progressors or ACs. Second, we found that nef alleles from LTNPs were less efficient in CD4 downregulation than those of progressors or ACs. Third, all nef alleles from LTNPs, progressors, and ACs reduced the cell surface expression of major histocompatibility complex class I to a similar level. Last, there was no correlation between Hck-binding activity of Nef and clinical grouping. In conclusion, we detected inefficient enhancement of HIV-1 infectivity and CD4 downregulation by HIV-1 nef alleles of LTNPs. It awaits further study to conclude that these characteristics of nef alleles are the cause or the consequence of the long-term nonprogression after HIV-1 infection.


Pulmonary hypertension-targeted therapies in heart failure: A systematic review and meta-analysis.
Pulmonary hypertension (PH) due to left heart failure (HF) is the most common form of PH. However, treatment is unclear because there are conflicting results about safety and efficacy of PH-targeted therapies. To assess the effects of PH-targeted therapy on exercise capacity in HF patients. MEDLINE, EMBASE and the Cochrane Library were searched from January 1990 to July 2017 for randomized controlled trials comparing PH-targeted therapies to conventional therapy in HF. The primary outcome was to assess the effects on exercise capacity. Secondary outcomes included mortality, hospitalisation, NT-proBNP levels, echocardiographic and hemodynamics parameters and discontinuation rate. 22 studies were included (n = 5448), including 3, 8 and 11 studies with low, high and unknown risk of bias, respectively. PH-targeted therapies were associated with an improvement of exercise capacity (standardized mean difference 0.29;95%CI:0.08-0.50, p = 0.006). Pre-specified subgroup analyses found that this improvement was predominantly observed in studies evaluating phosphodiesterase-5 inhibitors and prostanoids and in patients with reduced ejection fraction. Moreover, systolic pulmonary artery pressure measured by echocardiography was improved (mean difference: -7.5mmHg; [95%CI]: -14.9,-0.1, p = 0.05), which was also entirely driven by studies evaluating phosphodiesterase-5 inhibitors. However, PH-targeted therapies were associated with an increased treatment discontinuation rates and a potential increase in mortality compared to standard treatment. In conclusion, PH-targeted therapies and especially phosphodiesterase-5 inhibitors may improve exercise capacity in patients with HF. However, an increase in adverse outcomes was likely. Moreover, most studies were at high or unknown risk of bias, precluding confident conclusions about the effects of PH-targeted therapies.


Photoredox Catalysis in Organic Chemistry.
In recent years, photoredox catalysis has come to the forefront in organic chemistry as a powerful strategy for the activation of small molecules. In a general sense, these approaches rely on the ability of metal complexes and organic dyes to convert visible light into chemical energy by engaging in single-electron transfer with organic substrates, thereby generating reactive intermediates. In this Perspective, we highlight the unique ability of photoredox catalysis to expedite the development of completely new reaction mechanisms, with particular emphasis placed on multicatalytic strategies that enable the construction of challenging carbon-carbon and carbon-heteroatom bonds.


Imatinib and its combination with 2,5-dimethyl-celecoxibinduces apoptosis of human HT-29 colorectal cancer cells.
Mono-targeting by imatinib as a main antitumor agent does not always accomplish complete cancer suppression. 2,5-dimethyl-celecoxib (DMC) is a close structural analog of the selective cyclooxygenase-2 (COX-2) inhibitor, celecoxib, that lacks COX-2 inhibitory function. In this study, we aimed to show the apoptotic effects of imatinib in combination with DMC in human HT-29 colorectal cancer (CRC) cells. HT-29 CRC cells were treated with IC50 dose of imatinib (6.60 μM), DMC (23.45 μM), and their combination (half dose of IC50) for 24 h. The caspase-3 activity was estimated with colorimetric kit. The caspase-3 gene expression was evaluated by real-time PCR method. There was a significant up-regulation in caspase-3 enzyme activity and caspase-3 expression by imatinib and its half dose combination with DMC as compared to control. As a summary, the results of this study strongly suggest that half dose combination of imatinib with DMC induced apoptosis as potent as full dose imatinib in human HT-29 CRC cells, while minimizing undesired side effects related to imatinib mono-therapy. This study also pointed towards possible caspase-dependent actions of imatinib and DMC.


Autoradiographic determination of regional cerebral blood flow during hypoglycemia in newborn dogs.
To ascertain the regional cerebral blood flow (CBF) responses to hypoglycemia, nine newborn dogs were treated with insulin to blood glucose concentrations ranging from 1 to 35 mg/dl (mean 22 mg/dl). Systemic physiologic monitoring revealed no differences in mean arterial blood pressure, heart rate, paO2, paCO2, pHa, or blood lactate in the hypoglycemis animals and five normoglycemic controls. Significant increases in CBF occurred in 17 of 20 analyzed structures of brain in the hypoglycemic puppies, ranging from 158 to 446% of the normoglyycemic values. The percent increases in CBF were greatest in brainstem structures compared to other major regions of brain. A positive correlation existed between mean arterial blood pressure and cerebral cortical blood flow, suggesting a loss of CBF autoregulation during hypoglycemia. The pathophysiologic mechanism for the elevations in regional CBF might relate to stimulation of beta-adrenergic receptors in brain, as has been shown in adults.


Effects of Type 1 Diabetes Mellitus on Linear Growth: A Comprehensive Review.
Type 1 diabetes mellitus (T1DM) has a significant effect on the growth of children. The disease has a negative effect on growth when considered in relation to the time period and metabolic control. Studies in this review have suggested debilitated growth in children with T1DM and have a few anomalies in the growth hormone (GH)-insulin-like growth factor-1 (IGF-1) axis when compared to fit children. Some studies show that children with T1DM were taller before the onset of the disease and during early diagnosis. Moreover, the linear growth depends on the interaction between the gonadotropin hormone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and sex steroid hormones axis and GH-IGF-1; there's a rise in GH during puberty, which has an effect on the estrogen and testosterone, which leads to the pulsatile secretion of GH, this increment leads to insulin resistance. These studies suggest short stature in girls, and some suggest in both. The final height in boys was unchanged, but a slight decline was observed in girls. This review aims to provide the latest understanding of impaired height in children with T1DM. The most accepted and effective treatment of impaired growth is the administration of long-acting insulin or continuous rapid-acting insulin. However, height was affected by the administration of good basal insulin at puberty and was unaffected by the continuous subcutaneous insulin injection. Hence, new technologies are the therapeutic regimen in children, especially the prepubertal age group; it will be interesting to see their effects on growth patterns in these children with T1DM.


Muscarinic receptors in the cochlear nucleus and auditory nerve of the guinea pig.
The specific-binding properties of l-[3H]quinuclidinyl benzilate, a muscarinic acetylcholine-receptor antagonist, were investigated in synaptic and other membrane preparations of the guinea pig cochlear nucleus and auditory nerve. Binding parameters for all experiments were consistent with a single binding site with a Hill coefficient of 1.0. The binding of the ligand was specific and of high affinity, with values of KD in the range of 30-80 pM. Bmax was 0.352 +/- 0.023 pmol/mg protein for the dorsal cochlear nucleus and 0.215 +/- 0.011 pmol/mg protein for the ventral cochlear nucleus. The dorsal cochlear nucleus/ventral cochlear nucleus ratio for density of muscarinic receptors (1.6/1.0) was maintained across two different buffer systems, which varied with respect to the inclusion of proteolysis inhibitors. The results for auditory nerve indicated a level of binding much below that of the cochlear nucleus, with Bmax = 0.052 +/- 0.011 pmol/mg protein. The results of specific-binding experiments for l-[3H]quinuclidinyl benzilate support a role for acetylcholine as a neurotransmitter in the cochlear nucleus. The greater density of muscarinic receptors in the dorsal cochlear nucleus may indicate greater cholinergic activity in the dorsal relative to the ventral cochlear nucleus.


Choroid Neovascularization Growth Prediction With Treatment Based on Reaction-Diffusion Model in 3-D OCT Images.
Choroid neovascularization (CNV) is caused by new blood vessels growing in the choroid and penetrating the bruch membrane. It is the major cause of vision disability in many retinal diseases. Though anti-vascular endothelial growth factor injection has proved to be effective for treating CNV, treatment planning is essential to ensure the efficacy while reducing the risk. For this purpose, we propose a CNV growth model based on longitudinal optical coherence tomography (OCT) images. The reaction-diffusion model is applied to simulate the growth and shrinkage of CNV volumes, and is solved by using the finite-element method. A fitted curve of the CNV growth/shrinkage rate is obtained by optimizing the growth parameters. Then, the trained parameters are applied to the predicted image to get the simulated image, which is compared with the validated image to evaluate the accuracy of prediction. The proposed method was tested on a dataset with seven patients in which each patient has 12 longitudinal OCT images. The resulted mean dice coefficient is 76.40% ± 8.20%. The experimental results show a promising step towards the image-guided patient-specific treatment.


External coincidence model for hypocotyl thermomorphogenesis.
High but nonstressful temperatures profoundly affect plant growth and developmental processes, termed thermomorphogenesis. Thermo-induced hypocotyl elongation is a typical thermomorphogenic trait, which contributes to cooling plant organs. It is known that external light signals and the circadian clock coordinate rhythmic hypocotyl growth. However, it was unclear how light, temperature, and circadian rhythms are harmonized during hypocotyl thermomorphogenesis. We have recently demonstrated that the E3 ubiquitin ligase CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1) is activated at warm temperatures. It is notable that warm temperatures induce the nuclear import of COP1, facilitating degradation of ELONGATED HYPOCOTYL 5 (HY5) and this biochemical event is uncoupled from light conditions. Furthermore, the thermo-induced HY5 protein turnover occurs independent of circadian rhythms, indicating that the COP1-HY5 module conveys warm temperature information. Meanwhile, the clock components, including CIRCADIAN CLOCK ASSOCIATED 1 (CCA1), convey timing information for the rhythmic thermomorphogenic growth. These molecular mechanisms enable a coincidence between warm temperature signaling and circadian rhythms, which explains the distinct rhythms of hypocotyl growth at warm temperatures.


Distribution and characterization of more than 1000 T-DNA tags in the genome of Brachypodium distachyon community standard line Bd21.
A collection of 4117 fertile T-DNA lines has been generated by Agrobacterium-mediated transformation of the diploid community standard line Bd21 of Brachypodium distachyon. The regions flanking the T-DNA left and right borders of the first 741 transformed plants were isolated by adapter-ligation PCR and sequenced. A total of 1005 genomic sequences (representing 44.1% of all flanking sequences retrieved) characterized 660 independent T-DNA loci assigned to a unique location in the Brachypodium genome sequence. Seventy-six percent of the fertile plant lines contained at least one anchored T-DNA locus (1.17 loci per tagged line on average). Analysis of the regions flanking both borders of the T-DNA increased the number of T-DNA loci tagged and the number of tagged lines by approximately 50% when compared to a single border analysis. T-DNA integration (2.4 insertions per Mb on average) was proportional to chromosome size, however, varied greatly along each chromosome with often low insertion level around centromeres. The frequency of insertion within transposable elements (5.3%) was fivefold lower than expected if random insertion would have occurred. More than half of the T-DNAs inserted in genic regions. On average, one gene could be tagged for every second fertile plant line produced and more than one plant line out of three contained a T-DNA insertion directly within or 500 bp around the coding sequence. Approximately, 60% of the genes tagged corresponded to expressed genes. The T-DNA lines generated by the BrachyTAG programme are available as a community resource and have been distributed internationally since 2008 via the BrachyTAG.org web site.


Managing adverse drug reactions: an orphan task.
Nurse prescribing initiatives have potential to impact on medication management for long-term conditions. Over time, the adverse effects of medications become increasingly onerous. This 'side-effect burden' is particularly heavy for users of antipsychotic medication. Although consensus exists that strategies are needed to alleviate these problems, currently, they are not clearly the responsibility of any one professional group. This paper explores the introduction of nurse-administered evaluation checklists, in relation to nurse prescribing initiatives and division of professional responsibilities for medication management. This was an observation study, with a quasi-experimental comparator group design, undertaken with clients receiving long-term antipsychotic medication. In both intervention and comparator groups, before and after introduction of evaluation checklists in the intervention group, 20 nurse-client interactions were observed. Problems actioned by the nurses, with and without the checklists, were compared. Stakeholders' views were sought concurrently. Implementation of evaluation checklists increased the numbers of adverse effects detected and actioned by nurses. They also served to apportion aspects of medication management between nurses and medical prescribers. Most actions taken by nurses to alleviate adverse effects concerned clients' physical health and advice on health-promotion. However, the nurses' interventions would have been more effective had they been able to supply clients with certain medicines either by prescribing from the Nurse Prescribers' Formulary or issuing under Patient Group Directions. For some clients, ameliorating the adverse effects of medication would have involved changes to prescribed antipsychotic medication; here decisions were more equivocal. The identification of previously unattended problems, together with the views of service users, suggests that empowering nurses to address the 'care gaps' in medication management may benefit service users. The 'checklist evaluation' approach warrants further investigation, ideally in conjunction with nurse prescribing initiatives.


[What can be expected today of pharmacotherapy in the Alcohol Use Disorders?].
During the last past years, numerous drug have been proposed to treat Alcohol Use Disorders. Besides classical drugs as acomprosate or naltrexone, new compounds are developed in this new indication. They are used in substitution therapies (baclofen), either when the aim of the treatment is total abstinence from alcohol or as an aid for craving reduction facilitating a "controlled drinking", or also for the maintaining of abstinence (nalmefene). Those drugs, availaible in diferent countries, are now marketed in France (nalmefene). As yet, baclofen may be prescribed in France by the mean of a Temporary Utilisation Recommandation, according to the settlement of the National Medicament Agency. Despite the emphasis of some spectacular effects of baclofen, highly publicised by the media and some enthousiastic practitioners, the drug dosage/frequency has to be assessed by two ongoing controlled studies. The pharmacotherapy remains, however, only one element in the treatment of alcoholism, a complex biopsychosocial disorder. Various forms of psychotherapy remain necessary, the pharmacotherapy being only one, sometimes useful, additionnal treatment.


Clinicopathological roles of alterations of tumor suppressor gene p16 in papillary thyroid carcinoma.
Alterations of the p16 gene are common in human cancers, but their roles in thyroid cancers have not been clearly defined. The aim of the present study was to investigate the clinicopathological roles of the p16 gene in papillary thyroid carcinoma (PTC). p16 gene alterations were investigated in 44 patients with PTC (9 men, 35 women) by immunohistochemistry, reverse transcriptase-polymerase chain reaction and methylation-specific polymerase chain reaction. The findings were correlated with their clinicopathological features. p16 protein expression, mRNA alterations, and promoter methylation were detected in 89% (n = 39), 77% (n = 33), and 41% (n = 18) of patients with PTC, respectively. There was no marked relationship between p16 protein expression, mRNA alteration, and promoter methylation. In follicular variant of PTC (FVPTC), there was a frequent lack of p16 protein expression and promoter methylation. PTCs showing p16 promoter methylation were often associated with a high AMES (age, metastasis to distant sites, extrathyroidal invasion, size) risk group and advanced pTNM (tumor-lymph node-metastasis) stages. p16 gene alterations are common and correlate with histological features and biological aggressiveness in PTC, suggesting that they might play an important role in its pathogenesis.


Quality of life with diabetes-associated foot complications: comparison between lower-limb amputation and chronic foot ulceration.
Diabetic foot complications result in huge costs for both society and individual patients. Because our team performs numerous amputations each year for complicated diabetic foot ulcers, we conducted a study comparing the quality of life of diabetic amputees with a non-amputee group experiencing a diabetic foot ulcer. The aim of this study was to get better comprehension of the influence of amputation on physical and social aspects of our patients' quality of life. This study evaluated the influence of amputation for a diabetic foot ulcer on quality of life. We compared patients having experienced an amputation for a diabetic foot ulcer at least 1 year before the study, and outpatients experiencing regular visits for a current foot ulcer with no previous history of amputation. Quality of life was reported using the Medical Outcome Study Short Form 36 item health survey (MOS SF-36). Most of the chronic ulcers were neuroischemic (8/9). Except for the bodily pain, which was significantly higher in the ulcer group, no difference was found between the amputee and the ulceration-group, when considering the different items of the MOS-SF 36 scales. The ulceration-group had significantly more physical limitations and pain than the toe-or-transmetatarsal-amputation-group, whereas physical limitations were identical between the transtibial-amputation-group and the ulceration-group. Median scores were quite low in both groups, reflecting strong social and psychological consequences of diabetic foot ulcers. Global prognosis was bad with 56% of the amputees having experienced another major cardiovascular event within 20 months after amputation. Better understanding of the consequences of diabetic foot complications is important for the general population and especially general practitioners. Psychological evaluation and support is important before and after amputation since it is a traumatic step for patients.


The Public Health Challenge of Consumer Non-Compliance to Toy Product Recalls and Proposed Solutions.
This paper addresses the public health issue of toy product recalls in the United States, an under-addressed topic in scholarly literature, yet highly relevant to the prevention of pediatric injuries. Toy-related injuries led to 274,000 emergency room visits and seven fatalities in 2016 in the United States, and toy-related injury rates have remained stable over the last five years despite declining incidences of recalls. While dangerous toys not being recalled and the misuse of "safe" products are possible contributing factors, consumer non-response to recall notices also contributes to unintentional child injury from dangerous toys. We discuss the process of recalling toys, and the role of the U.S. Consumer Product Safety Commission in that process. We also review potential factors behind significant consumer non-response to recall notifications, citing economic and psychological theories as explanations for the actions of multiple stakeholders in the recall process. We close by proposing reforms at the regulatory, consumer, and retailer levels that might boost compliance with recall notifications and ultimately reduce injury morbidity and mortality.


Rosai Dorfman syndrome with extranodal manifestation.
Rosai Dorfman Syndrome (RDS) is a benign condition and a rare cause of cervical lymphadenopathy. It usually occurs in the first decade of life and manifest as massive enlargement of cervical lymph nodes. The disease has a benign course and involvement of the nasal cavity as an extranodal site is exceptional. A 22-year-old male presented as progressive massive bilateral cervical lymphadenopathy accompanied with nasal obstruction and occasional episodes of epistaxis. A FNAC from cervical lymph node and biopsy from nasal mass was compatible with RDS.


Ultra-thin circular polarization analyzer based on the metal rectangular split-ring resonators.
We propose an ultra-thin metasurface of the metal rectangular split-ring resonators (MRSRR) array which can modulate and analyze the wavefront of circularly polarized light efficiently. An incident circularly polarized light could be converted into the corresponding cross-polarized light which would be bent to ± 23° at a wavelength of 808 nm for the normal incidence. And a linearly polarized light would be decomposed into two lights of left and right-handed circular polarizations in the directions of ∓23° respectively. These phenomena have also been observed at 1200 nm with different geometric parameters. And these results depend on controlling the optical-axis profile of the resonators in a subwavelength scale by precisely modulating two degrees of freedom in our nanostructures.


General method for the palladium-catalyzed allylation of aliphatic alcohols.
A palladium catalysis-mediated approach to coupling aliphatic alcohols with allyl carbonates has been developed. The method allows for the allylation of primary, secondary, and tertiary alcohols efficiently under mild conditions. Limitations were explored as well as the asymmetric application of the chemistry. Regiochemical and olefin geometry was controlled in the coupling of unsymmetrical allylating agents. Transient allyl carbonates were observed in the coupling, which comprised the trans-carboxylation of the allyl-carbonate with the requisite alcohol.


Research in nursing education: assumptions and priorities.
The purposes of this study were: to identify assumptions about the nature of research in nursing education, and to identify and rank order critical research questions regarding nursing education. The Delphi survey technique was used with 121 nurse educators responding to three survey rounds. The panel concurred with the assumptions that research in nursing education can and should meet criteria for scientific merit, should not be viewed as secondary in importance to nursing practice research, should emphasize the clinical nature of nursing, and needs to be less fragmented. Priorities for research included the following topics: integration of research findings into nursing curricula, development of problem solving skills, approaches to clinical teaching, and level of practice of graduates of different basic preparations.


Exogenous gangliosides, neuronal plasticity and repair, and the neurotrophins.
Gangliosides, a heterogeneous family of glycosphingolipids abundant in the brain, have been shown to affect neuronal plasticity during development, adulthood and aging. This review will examine old and recent evidence that exogenous gangliosides and in particular GM1, the prototype member of this family, exhibit multimodal neurotrophic effects. Since these compounds are a potential therapeutic tool for the treatment of various forms of acute or chronic neurodegenerative diseases, understanding the dynamic interplay of gangliosides and neuronal cells is essential in the effort to cure neurological disorders. Focus will be given to the novel and provocative hypothesis that gangliosides' neuroprotective properties may derive from their ability to mimic endogenous neurotrophic factors.


Recovery as perceived by people with schizophrenia, family members and health professionals: a grounded theory.
Advances in knowledge in the biomedical and psychosocial sciences have expanded our understanding of schizophrenia and of how it evolves in people living with it. These individuals are no longer viewed as being 'ill' and requiring long-term hospitalisation. We have come instead to have a much more positive view of them and of the role they can play in coming to terms both with their health condition and with society. In the majority of cases, schizophrenia sufferers have the potential to recover. The purpose of this study is to propose a theoretical explanation of recovery based on the concept of human responses put forward by the American Nurses' Association. Data were collected from 41 participants (16 people living with schizophrenia, 5 family members, 20 health professionals). Selection criteria required the people living with schizophrenia to be in stable health, see themselves as being in the process of recovery, and be able to speak about it. Family members were expected to have displayed a strong bond with their relative living with schizophrenia, and the health professionals to have had at least 3 years experience dealing with schizophrenia patients. The Grounded Theory approach was selected because it allows for diversified data sources to be used in the empirical study of a phenomenon. It is an appropriate approach for the conceptualization of complex phenomena and the development of middle-range theory. To ensure a variety of subjects were involved, semi-structured interviews were conducted in three different settings: a specialised psychiatric hospital, a self-help group, and a community setting. Seven categories emerged from the analysis and conceptualization: perceiving schizophrenia as a 'descent into hell'; igniting a spark of hope; developing insight; activating the instinct to fight back; discovering keys to well-being; maintaining a constant equilibrium between internal and external forces; and, finally, seeing light at the end of the tunnel. Comparison of these categories led to their being consolidated into a core category in which recovery is defined as a 'process involving intrinsic, non-linear progress that is primarily generated by the role as actor that the individual adopts to rebuild his or her sense of self and to manage the imbalance between internal and external forces with the objective of charting a path through the social world and regaining a sense of well-being on all biopsychosocial levels.' This study of recovery from schizophrenia is conceptualised from the nursing perspective: the concept of 'Human Responses' [American Nurses Association (ANA), 1980. Nursing: A Social Policy Statement. ANA, Kansas City, MO; American Association of Neuroscience Nurses (AANN's), 2001. AANN's Neuroscience Nursing: Human Responses to Neurologic Dysfunction, second ed. W. B. Saunders Company, Philadelphia]. It was possible to go beyond a descriptive analysis and bring out the dynamics of the process through a detailed, in-depth presentation of the recovery process. The theoretical explanation we have postulated is based on the inner resources of individuals diagnosed with schizophrenia and their potential to make a recovery.


Effect of undigested neutral detergent fiber content of alfalfa hay on lactating dairy cows: Feeding behavior, fiber digestibility, and lactation performance.
The objective of this study was to investigate the effects of 2 alfalfa hays differing in undigested neutral detergent fiber content and digestibility used as the main forage source in diets fed to high producing cows for Parmigiano-Reggiano cheese production. Diets were designed to have 2 different amounts of undigestible NDF [high (Hu) and low (Lu)], as determined by 240-h in vitro analysis (uNDF240). Alfalfa hay in vitro digestibility [% of amylase- and sodium sulfite-treated NDF with ash correction (aNDFom)] at 24 and 240 h was 40.2 and 31.2% and 53.6 and 45.7% for low- (LD) and high-digestibility (HD) hays, respectively. The 4 experimental diets (Hu-HD, Lu-HD, Hu-LD, and Lu-LD) contained 46.8, 36.8, 38.8, and 30.1% of alfalfa hay, respectively, 8.6% wheat straw, and 35.3% corn (50% flake and 50% meal; DM basis). Soy hulls and soybean meal were used to replace hay to balance protein and energy among diets. Eight multiparous Holstein cows (average milk production = 46.0 ± 5.2 kg/d, 101 ± 38 d in milk, and 662 ± 42 kg of average body weight) were assigned to a 4 × 4 Latin square design, with 2 wk of adaptation and a 1-wk collection period. Dry matter and water intake, rumination time, ruminal pH, and milk production and composition were measured. Diets and feces were analyzed for NDF on an organic matter basis (aNDFom), acid detergent fiber, acid detergent lignin, and uNDF240 to estimate total-tract fiber digestibility. Dry matter intake and rumination times were higher in HD diets compared with LD diets, regardless of forage amount. Rumination time was constant per unit of dry matter intake but differed when expressed as a function of uNDF240, aNDFom, or physically effective NDF intake. No differences were found among treatments on average ruminal pH, but the amount of time with pH <5.8 was lower in Hu-HD diets. Milk production and components were not different among diets. Total-tract aNDFom and potentially digestible neutral detergent fiber fraction digestibility was higher for the LD diets (88.3 versus 85.8% aNDFom in HD), for which lower feed intakes were also observed. The Hu-HD diet allowed greater dry matter intake, longer rumination time, and higher ruminal pH, suggesting that the limiting factor for dry matter intake is neutral detergent fiber digestibility and its relative rumen retention time.


Complete Genome Sequence of Southern tomato virus Identified in China Using Next-Generation Sequencing.
The complete genome sequence of Southern tomato virus (STV), a double-stranded RNA virus that affects tomato in China, was determined using small RNA deep sequencing. This Chinese isolate shares 99% sequence identity to other isolates from Mexico, France, Spain, and the United States. This is the first report of STV infecting tomatoes in Asia.


Mapping allosteric linkage to channel gating by extracellular domains in the human epithelial sodium channel.
The epithelial sodium channel (ENaC) mediates sodium absorption in lung, kidney, and colon epithelia. Channels in the ENaC/degenerin family possess an extracellular region that senses physicochemical changes in the extracellular milieu and allosterically regulates the channel opening. Proteolytic cleavage activates the ENaC opening, by the removal of specific segments in the finger domains of the α- and γ ENaC-subunits. Cleavage causes perturbations in the extracellular region that propagate to the channel gate. However, it is not known how the channel structure mediates the propagation of activation signals through the extracellular sensing domains. Here, to identify the structure-function determinants that mediate allosteric ENaC activation, we performed MD simulations, thiol modification of residues substituted by cysteine, and voltage-clamp electrophysiology recordings. Our simulations of an ENaC heterotetramer, α1βα2γ, in the proteolytically cleaved and uncleaved states revealed structural pathways in the α-subunit that are responsible for ENaC proteolytic activation. To validate these findings, we performed site-directed mutagenesis to introduce cysteine substitutions in the extracellular domains of the α-, β-, and γ ENaC-subunits. Insertion of a cysteine at the α-subunit Glu557 site, predicted to stabilize a closed state of ENaC, inhibited ENaC basal activity and retarded the kinetics of proteolytic activation by 2-fold. Our results suggest that the lower palm domain of αENaC is essential for ENaC activation. In conclusion, our integrated computational and experimental approach suggests key structure-function determinants for ENaC proteolytic activation and points toward a mechanistic model for the allosteric communication in the extracellular domains of the ENaC/degenerin family channels.


Determining the need for ethical review: a three-stage Delphi study.
The aims of the study were to explore expert opinion on the distinction between "research" and "audit", and to determine the need for review by a National Health Service (NHS) Research Ethics Committee (REC). Under current guidelines only "research" projects within the NHS require REC approval. Concerns have been expressed over difficulties in distinguishing between research and other types of project, and no existing guidelines appear to have been validated. The implications of this confusion include unnecessary REC applications, and crucially, the potential for ethically unsound projects to escape review. A three-stage Delphi method was chosen to explore expert opinion and develop consensus. Stage 1 comprised ten semi-structured interviews gathering opinion on distinguishing between types of project and how to determine need for ethical review. Stages 2 and 3 were questionnaires, asking 24 "experts" to rate levels of ethical concern and types of project for a series of questions. Anonymised responses from stage 2 were fed back in stage 3. The final responses were analysed for consensus. Of 46 questions, consensus was achieved for 14 (30.4%) for level of ethical concern and for 15 (32.6%) for type of project. Several ideas proved discriminatory for classifying the type of project and assessing level of ethical concern, and they can be used to develop an algorithm to determine need for ethical review. There was little relationship between assessment of the level of ethical concern and classification of the project. There was inconsistency in defining and classifying studies as something other than "research" or "audit".


Epidemiologic and clinical features of hidradenitis suppurativa.
Hidradenitis suppurativa (HS) is an inflammatory condition characterized by recurrent abscesses which may result in sinus tracts and dermal scarring. This article reviews current epidemiologic data on HS in diverse populations, including prevalence based on geography, age, gender, ethnicity, and details the spectrum of clinical features of hidradenitis suppurativa with discussion of disease severity and risk factors. Recently proposed HS diagnostic criteria are also presented.


Up-regulation of neurohemerythrin expression in the central nervous system of the medicinal leech, Hirudo medicinalis, following septic injury.
We report here some results of a proteomic analysis of changes in protein expression in the leech Hirudo medicinalis in response to septic injury. Comparison of two-dimensional protein gels revealed several significant differences between normal and experimental tissues. One protein found to be up-regulated after septic shock was identified, through a combination of Edman degradation, mass spectrometry, and molecular cloning, as a novel member of the hemerythrin family, a group of non-heme-iron oxygen transport proteins found in four invertebrate phyla: sipunculids, priapulids, brachiopods, and annelids. We found by in situ hybridization and immunocytochemistry that the new leech protein, which we have called neurohemerythrin, is indeed expressed in the leech central nervous system. Both message and protein were detected in the pair of large glia within the ganglionic neuropile, in the six packet glia that surround neuronal somata in each central ganglion, and in the bilateral pair of glia that separate axonal fascicles in the interganglionic connective nerves. No expression was detected in central neurons or in central nervous system microglia. Expression was also observed in many other, non-neuronal tissues in the body wall. Real-time PCR experiments suggest that neurohemerythrin is up-regulated posttranscriptionaly. We consider potential roles of neurohemerythrin, associated with its ability to bind oxygen and iron, in the innate immune response of the leech nervous system to bacterial invasion.


Infrequent Clinical Assessment of Chronic Hepatitis B Patients in United States General Healthcare Settings.
Among 2338 chronic hepatitis B patients followed during 2006-2013 in the Chronic Hepatitis Cohort Study, 78% had ≥1 alanine aminotransferase and 37% had ≥1 hepatitis B virus DNA level assessed annually. Among cirrhotic patients, 46% never had hepatic imaging. Patients in this cohort were insufficiently monitored for disease activity and hepatocellular carcinoma.


Repetition suppression in transcranial magnetic stimulation-induced motor-evoked potentials is modulated by cortical inhibition.
Transcranial magnetic stimulation (TMS) can be applied to modulate cortical phenomena. The modulation effect is dependent on the applied stimulation frequency. Repetition suppression (RS) has been demonstrated in the motor system using TMS with short suprathreshold 1-Hz stimulation trains repeated at long inter-train intervals. RS has been reported to occur in the resting motor-evoked potentials (MEPs) with respect to the first pulse in a train of stimuli. Although this RS in the motor system has been described in previous studies, the neuronal origin of the phenomenon is still poorly understood. The present study evaluated RS in three TMS-induced motor responses; resting and active MEPs as well as corticospinal silent periods (SPs) in order to clarify the mechanism behind TMS-induced RS. We studied 10 healthy right-handed subjects using trains of four stimuli with stimulation intensities of 120% of the resting motor threshold (rMT) and 120% of the silent period threshold for an SP duration of 30 ms (SPT30). Inter-trial interval was 20s, with a 1-s inter-stimulus interval within the trains. We confirmed that RS appears in resting MEPs (p < 0.001), whereas active MEPs did not exhibit RS (p > 0.792). SPs, on the contrary, lengthened (p < 0.001) indicating modulation of cortical inhibition. The effects of the two stimulation intensities exhibited a similar trend; however, the SPT30 evoked a more profound inhibitory effect compared to that achieved by rMT. Moreover, the resting MEP amplitudes and SP durations correlated (rho ⩽ -0.674, p < 0.001) and the pre-TMS EMG level did not differ between stimuli in resting MEPs (F = 0.0, p ⩾ 0.999). These results imply that the attenuation of response size seen in resting MEPs might originate from increasing activity of inhibitory GABAergic interneurons which relay the characteristics of SPs.


Crohn's disease in the elderly: Clinical presentation and manifestations from a tertiary referral center in Turkey.
There is no precise consensus at present on age to define elderly patients with inflammatory bowel disease (IBD), but recently, age of more than 60 years has been widely accepted. Characteristics of IBD in the elderly are somewhat different from what is seen in younger patients. The elderly have milder disease activity, and therapeutic options are fewer because of their age and features such as comorbidities, drug interactions, and loss of organ function. There are few reports on Crohn's disease in the elderly. Herein, first report on this topic with respect to population of this country is presented. Characteristics of 95 patients with Crohn's disease, who were over age 60 from 3125 patients with IBD treated in our clinic between 1996 and 2015 were analyzed. Research was performed using patient files, and outpatient clinic visits, when possible. Median age of the group was 66 years, and male:female ratio was 1.6. Of the total, 48.4% of the patients had colonic disease, 37.9% had ileocolonic disease, and 13.7% had small bowel disease. Data indicated that 23.1% of patients had undergone surgical procedures, which were primarily right hemicolectomy and ileotransversostomy. Disease was most often managed with mesalazine or azathioprine. It was also determined that 12.6% patients had 2 or more comorbidities, and findings indicated coronary heart disease and hypertension were most prevalent. Analysis revealed similar features in characteristics of disease compared with recent knowledge reported in the literature. This is the first report from our country to describe Crohn's disease in the elderly population, and the number of patients is sufficient to provide general information about this group.


Guardianship primavera: a first look at factors associated with having a legal guardian using a nationally representative sample of community-dwelling adults.
Although guardianship is an intrusive intervention that usually removes an adult's basic civil rights, studies of factors that place adults at risk for guardianship have largely been based on small studies of court files. While important and informative, these studies do not allow us to draw anything but tentative conclusions on risk factors for guardianship. The purpose of this article is to examine risk factors for having a legal guardian using a nationally representative sample for the first time. Logistic regression was conducted on the probability of having a legal guardian, using the Andersen model of health care utilization adapted for factors implied by the guardianship literature. The National Health Interview Supplement on Disability (1995) sample consisted of 65,013 adults aged 19 and older, and a sub-sample aged 60 and older (n = 13,784). Results indicate, first, that the prevalence of guardianship in community-dwelling adults is 0.3 percent, or over 750,000 people. Second, particularly for older adults, increasing age, having physical or emotional limitations, a small family network, and not living with a spouse are associated with having a guardian. Decreasing size of family networks and increasing marital disruption in future cohorts of older adults may suggest increasing need for legal guardianship. Further study should be conducted to replicate these findings in other large data sets and in extensive community studies.


Role of tissue factor in thrombosis in antiphospholipid antibody syndrome.
Antiphospholipid syndrome (APS) is an acquired autoimmune disorder defined by the presence of an antiphospholipid antibody (aPL) and the occurrence of at least one associated clinical condition that includes venous thrombosis, arterial thrombosis or pregnancy morbidity. The aPL detected in APS have long been thought to have a direct prothrombotic effect in vivo. However, the pathophysiology underlying their coagulopathic effect has not been defined. Emerging data suggest a role for the procoagulant protein tissue factor (TF). In this review we provide an overview of TF, describe mouse models used in the evaluation of the role of TF in thrombosis, as well as summarize recent work on TF and APS.


Ferroptosis, a Potential Therapeutic Target in Alzheimer's Disease.
Cell death is a common phenomenon in the progression of Alzheimer's disease (AD). However, the mechanism of triggering the death of neuronal cells remains unclear. Ferroptosis is an iron-dependent lipid peroxidation-driven cell death and emerging evidences have demonstrated the involvement of ferroptosis in the pathological process of AD. Moreover, several hallmarks of AD pathogenesis were consistent with the characteristics of ferroptosis, such as excess iron accumulation, elevated lipid peroxides, and reactive oxygen species (ROS), reduced glutathione (GSH), and glutathione peroxidase 4 (GPX4) levels. Besides, some ferroptosis inhibitors can relieve AD-related pathological symptoms in AD mice and exhibit potential clinical benefits in AD patients. Therefore, ferroptosis is gradually being considered as a distinct cell death mechanism in the pathogenesis of AD. However, direct evidence is still lacking. In this review, we summarize the features of ferroptosis in AD, its underlying mechanisms in AD pathology, and review the application of ferroptosis inhibitors in both AD clinical trials and mice/cell models, to provide valuable information for future treatment and prevention of this devastating disease.


Dose-response relationship between objective measures of histamine-induced weals and dose of terfenadine.
Terfenadine is a safe non-sedative H1-receptor antagonist. This study aimed to quantify the relative reduction in weal and flare area, thickness and erythema at 4, 8, 12 and 24 h following a single but variable oral dose of terfenadine compared with pre-treatment measurements, in order to compare the dose-effect relationship and time course of the different dosages. In a double-blind randomized cross-over study, 12 healthy volunteers were given 60, 120 or 240 mg of terfenadine or placebo. Twenty micrograms of histamine acid phosphate was then injected intradermally at 4, 8, 12 and 24 h. The weal and flare areas were measured by planimetry, the thickness of the weal by an A-scan pulsed ultrasound device and the redness of both the weal and flare by an erythema-meter. A definite dose-response relationship was demonstrated between the weal and flare areas and the three active treatments. For the weal area, there was a significant difference between 60 mg and 240 mg of terfenadine at 4 h (p less than 0.01), at 8 and 12 h (p less than 0.05). For the flare area there was a similar significant difference at 4 h (p less than 0.01) and at 8 h (p less than 0.05). A dose-response relationship was demonstrated between weal erythema and 120 mg or 240 mg and 60 mg of terfenadine (p less than 0.05). There was a correlation between the plasma levels of the major metabolite and the initial dose of terfenadine, demonstrating their expected proportionality. This metabolite was also demonstrated in tissue fluid.


Phase-locking of magnetic islands diagnosed by ECE-imaging.
Millimeter-wave imaging diagnostics identify phase-locking and the satisfaction of 3-wave coupling selection criteria among multiple magnetic island chains by providing a localized, internal measurement of the 2D power spectral density, S(ω, kpol). In high-confinement tokamak discharges, these interactions impact both plasma rotation and tearing stability. Nonlinear coupling among neoclassical tearing modes of different n-number, with islands not satisfying the poloidal mode number selection criterion ⟨m, m('), m - m(')⟩, contributes to a reduction in core rotation and flow shear in the vicinity of the modes.


Progress and prospects for quantum dots in a well infrared photodetectors.
Over the past fifteen years, there has been significant interest in developing intersubband quantum dot (QD) detectors for the mid-(MWIR) and long-wave infrared (LWIR) regimes. This class of detectors is generally referred to as quantum dot infrared photodetectors, or QDIPs. At present, one of the leading technologies is that of the quantum dots-in-a-well infrared photodetector, called a DWELL-IP or just a DWELL detector. The DWELL name comes from the active region's structure, which consists of a layer of quantum dots imbedded in (or in some cases grown on) a quantum well. This dot/well combination is similarly surrounded by a barrier material. Here, we identify the major players and their contributions to the evolution of the DWELL-IP. While this dot/well/barrier material combination originally consisted of InAs/InGaAs/GaAs, the materials used has widened in recent years. This paper reviews the progress to date for this quickly advancing field. Some of these advancements have come from the additional focus that has been brought to bear on the physical understanding and experimental mechanics of the structure itself. Explorations into the multi-spectral nature of these detectors have also created unique applications for these detectors. This type of QDIP is now becoming the dominant detector of its class and is quickly heading for parity with quantum well infrared photodetectors (QWIPs) that are presently commercially dominant. Given the potential utility of the infrared spectrum for applications in medicine, military, industrial, and academic fields the DWELL-IPs potential to be an inexpensive, versatile, multi-spectral, infrared detector indicates it has a bright future.


Human pituitary growth hormone (hGH) and Creutzfeldt-Jakob disease: results of an epidemiological survey in France, 1986.
An epidemiological inquiry has been done in France after the notification in the USA and England of four cases of Creutzfeldt-Jakob disease in patients previously treated with hGH. Between 1959, when hGH treatment in France was started, and August 1985, the date the survey began, 1698 patients were registered for treatment. Current information (less than three months old) was obtained for 1620 patients (95.4%). Death was reported in 31 patients, but none could be related to Creutzfeldt-Jakob or similar disease. Pathological events were observed in 213 living patients (13.1%). Among them, four were diseases classified as possibly related to a viral infection. The first case had acute lymphoid leukaemia; the second case had polyradiculoneuritis associated with hepatitis. In both cases the disease resolved completely. Two other patients had acute encephalitis which started less than two years after the onset of treatment and which resolved spontaneously. Even though the acute evolution and the spontaneous clinical recovery are not consistent with Creutzfeldt-Jakob disease, a relationship with hGH therapy could not be completely excluded. Finally, five treated children had later malignancies which raises the question of the long-term secondary effects of hGH upon cellular proliferation.


Conservative management of upper eyelid entropion.
The authors report for the first time two cases of upper eyelid entropion secondary to neonatal conjunctivitis that resolved spontaneously following the insertion of a bandage contact lens. Previous reports advocate early surgical intervention to correct the eyelid abnormality and prevent any permanent corneal scarring and visual loss.


In vivo and in vitro interaction of 1,2-dichlorobenzene with nucleic acids and proteins of mice and rats.
Twenty-two hours after i.p. injection into male Wistar rats and BALB/c mice, 1,2-dichlorobenzene (1,2-DCB) was covalently bound to DNA, RNA, and proteins of liver, kidney, lung and stomach. The covalent binding index to liver DNA was typical of carcinogens classified as weak initiators. The enzyme-mediated in vitro interaction of 1,2-DCB with calf thymus DNA of synthetic polyribonucleotides was carried out by a microsomal mixed-function oxidase system and microsomal GSH-transferases, which seemed to be effective only in liver and lung of rat and mouse. Cytosolic GSH-transferases played a minor role in 1,2-DCB bioactivation. The latter finding provides the first evidence of 1,2-DCB genotoxicity in mammalian cells. The type of halide, the number of halosubstituents and their spatial disposition on the benzene ring are the major determinants of halobenzenes activability to intermediate(s) capable of interacting covalently with DNA and other macromolecules in biologic systems.