Keeping in touch with children after separation: the point of view of fathers.
The amount of father-child contact after separation is closely linked to the probability that father fulfill their financial obligations towards their children. Determining the factors that encourage this contact is, therefore, crucial to the process of reducing the risk of poverty to which children of separated parents are exposed. Based on data collected from fathers at the 1995 Canadian General Social Survey of the Family, this paper uses multi-level regression analysis to identify factors associated with higher levels of contact between fathers and children, including socio-demographic characteristics of children and fathers, variables associated with attitudes, and fathers' satisfaction with custody and access arrangements.


Ultrasonography in pericardial effusion.
Four cases of pericardial effusion diagnosed by echocardiography are reported. While one of the four cases was referred for echocardiography with a diagnosis of pericardial effusion, the other three patients were selected for echocardiography on the basis of cardiomegaly demonstrated in plain x-ray chest examination. Real time echocardiography was considered to be most rapid, safe, convenient, accurate and least invasive method of diagnosing pericardial effusion.


Identifying risk factors for missed compartment syndrome in patients with tibia shaft fractures: An analysis of the national trauma data bank.
Acute compartment syndrome (CS) is a common complication of tibia shaft fractures (TSFs), and occurs when the pressure inside a myofascial compartment rises and impairs tissue perfusion. If treatment is delayed due to a missed diagnosis, amputation or permanent loss of function can result. This study aims to determine the incidence, clinical associations, and risk factors for missed CS following surgical stabilization of tibia shaft fractures (TSFs) using data from the National Trauma Data Bank (NTDB). NTDB data files from 2007 to 2016 were accessed to collect information on patients undergoing surgical fixation of TSFs. Patients with an Injury Severity Score (ISS) > 15 or inferred Gustilo-Anderson IIIB/IIIC fractures were excluded to create a more homogenous sample of lower-grade TSFs. Compartment syndrome that was originally missed leading to late intervention was the main outcome under investigation. Bivariate tests were used to assess the relationships between missed CS and the preoperative variables. If a variable and a complication had an association with a P ≤ 0.2, it was included in a multivariate logistic regression model. A total of 184,612 patients met our inclusion criteria, and 1,269 patients (0.76%) had a missed CS diagnosis. Bivariate analysis demonstrated that male gender had a significant positive association with a missed CS diagnosis, while older age had a significant negative association (odds ratio [OR] = 2.17, 0.99; P < 0.001). Multivariate analysis revealed that male gender was the most significant independent risk factor for a missed diagnosis of compartment syndrome (OR = 1.84, P < 0.00001), followed by alcoholism, penetrating trauma, and smoking (OR = 1.51, 1.46, 1.43; P < 0.02). The only significant protective factor was open fracture (OR = 0.70, P < 0.0001). Our research identified several significant risk factors for missed CS after TSF, as well as positive and negative associations. Male gender, age, and lifestyle choices such as alcohol use and smoking conferred increased risks. These variables may assist physicians in identifying at-risk patients who may benefit from increased monitoring, and potentially prevent the high morbidity associated with this condition.


Heat-induced and spontaneous expression of Hsp70.1Luciferase transgene copies localized on Xp22 in female bovine cells.
Expression of several copies of the heat-inducible Hsp70.1Luciferase (LUC) transgene inserted at a single X chromosome locus of a bull (Bos taurus) was assessed in females after X-chromosome inactivation (XCI). Furthermore, impact of the chromosomal environment on the spontaneous expression of these transgene copies before XCI was studied during early development in embryos obtained after in vitro fertilization (IVF), when the locus was carried by the X chromosome inherited from the bull, and after somatic cell nuclear transfer (SCNT) cloning, when the locus could be carried by the inactive Xi or the active Xa chromosome in a female donor cell, or by the (active) X in a male donor cell. Transgene copies were mapped to bovine Xp22. In XXLUC female fibroblasts, i.e. after random XCI, the proportions of late-replicating inactive and early-replicating active XLUC chromosomes were not biased and the proportion of cells displaying an increase in the level of immunostained luciferase protein after heat-shock induction was similar to that in male fibroblasts. Spontaneous transgene expression occurred at the 8-16-cell stage both in transgenic (female) embryos obtained after IVF and in male and female embryos obtained after SCNT. The XLUC chromosome is normally inactivated but at least part of the inactivated X-linked Hsp70.1Luciferase transgene copies remains heat-inducible after random XCI in somatic cells. Before XCI, the profile of the transgenes' spontaneous expression is independent of the epigenetic origin of the XLUC chromosome since it is similar in IVF female, SCNT male and SCNT female embryos.


Loss of factor VIII activity during storage in PVC containers due to adsorption.
Recombinant factor VIII concentrates are stable when administered in a reconstituted form according to the manufacturer's specifications, and undiluted via infusion with syringe mini-pumps. However many Haemophilia centres administer recombinant factor VIII further diluted in intravenous fluids for greater ease of administration. To investigate the stability of recombinant factor VIII during administration as a diluted infusion, reconstituted factor VIII was stored in polyvinylchloride (PVC) mini-bags undiluted (146 IU mL-1) and at factor VIII concentrations of 10 IU mL-1 and 2 IU mL-1. After 48 h of storage at room temperature in PVC mini-bags, the recoveries of factor VIII activity were 41.9% of the initial activity for the undiluted (146 IU mL-1) product and 43.7% of the initial activity for factor VIII diluted to 10 IU mL-1. For factor VIII diluted to 2 IU mL-1, the amount of factor VIII activity remaining at 48 h was only 1.8% of the initial activity. In contrast, 100% of factor VIII activity was recovered after 48 h when undiluted reconstituted product (146 IU mL-1) was stored in a syringe. To investigate the mechanism of factor VIII activity loss during storage, factor VIII samples collected after 0, 3 and 48 h of storage were analysed by immunoblotting with factor VIII antibodies. No evidence of factor VIII proteolytic degradation during storage was found, however, large amounts of factor VIII antigen were recovered from the empty PVC mini-bags following elution with denaturing detergent. We conclude that clinically significant losses of factor VIII activity occur during storage in PVC mini-bags and that the loss of activity is most likely due to protein adsorption onto the plastic surface. This loss of factor VIII activity during storage in PVC containers may substantially affect the safety and potential cost savings of administering recombinant factor VIII by continuous infusion.


A randomized trial assessing the effects of 4 weeks of daily stretching on ankle mobility in patients with spinal cord injuries.
To determine the effect of 4 weeks of 30 minutes of daily stretching on ankle mobility in patients with recent spinal cord injuries (SCIs). Assessor-blinded randomized controlled trial. Two spinal injury units in Sydney, Australia. Consecutive sample of 14 recently injured patients with paraplegia and quadriplegia. Treated ankles were stretched continuously into dorsiflexion with a torque of 7.5 N x m for 30 minutes each weekday for 4 weeks. Contralateral ankles received no stretches. Passive torque-angle curves for both ankles were obtained at study commencement, then at weeks 2, 4, and 5 (ie, during, at the end of, and 1 week after the stretching program). Torque-angle measurements were obtained with the knee extended and flexed. Mean values for parameters (baseline angle, angle at 10 N x m, slope) describing the characteristics of the torque-angle curves were derived for each knee position. Changes from pretest to each subsequent test were calculated, as well as 95% confidence intervals (CIs) for differences in these changes between stretched and controlled ankles. The stretching intervention did not significantly change any of the 3 parameters describing the torque-angle curves of the ankle in either knee position. At the beginning of the study, the mean (+/-SD) angles obtained with the application of a standardized torque with the knee extended for the control and stretch ankles were 105 degrees (+/- 10.4 degrees) and 106 degrees (+/- 9.8 degrees), respectively. After 4 weeks, these values were 106 degrees (+/- 10.6 degrees) and 107 degrees (+/- 10.6 degrees) (mean difference in change of angle = 0 degrees; 95% CI, -3.3 degrees to 3.3 degrees). Thirty minutes of daily stretching for 4 weeks does not significantly change ankle mobility in recently injured patients with SCIs.


A double-blind comparison of diflunisal and aspirin in the treatment of post-operative pain after episiotomy.
A double-blind randomized trial was carried out in 161 primiparous women suffering from moderate to severe post-episiotomy pain to compare the analgesic efficacy of single doses of diflunisal (125 mg, 250 mg, of 500 mg), aspirin (600 mg), and placebo. The results of pain rating assessments made before and at hourly intervals after drug administration showed that both the active drugs were more effective than placebo and produced similar pain relief over the first 4 hours. The analgesic efficacy of aspirin tailed off after 4 hours but pain relief with 500 mg diflunisal was still evident after 8 hours. Over 65% of patients in the diflunisal group had effective relief of pain at 8 hours whereas there was no significant difference between the aspirin and placebo-treated groups by the seventh and eighth hour.


Nutritional status and health care costs for the elderly living in municipal residential homes--an intervention study.
The aim was to study the effect of individualised meals on nutritional status among older people living in municipal residential homes and to compare the results with a control group. An additional aim was to estimate direct health care costs for both groups. Six different municipal residential homes in the south-east of Sweden. Older people living in three residential homes constituted the intervention group n=42 and the rest constituted the control group n=67. A multifaceted intervention design was used. Based on an interview with staff a tailored education programme about nutritional care, including both theoretical and practical issues, was carried through to staff in the intervention group. Nutritional status among the elderly was measured by Mini Nutritional Assessment (MNA), individualised meals were offered to the residents based on the results of the MNA. Staff in the control group only received education on how to measure MNA and the residents followed the usual meal routines. Nutritional status was measured by MNA at baseline and after 3 months. Cost data on health care visits during 2007 were collected from the Cost Per Patient database. Nutritional status improved and body weight increased after 3 months in the intervention group. Thus, primary health care costs constituted about 80% of the total median cost in the intervention group and about 55% in the control group. With improved knowledge the staff could offer the elderly more individualised meals. One of their future challenges is to recognise and assess nutritional status among this group. If malnutrition could be prevented health care costs should be reduced.


Efficacy of postprocedural anticoagulation after primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: A post-hoc analysis of the randomized INNOVATION trial.
There exists controversy on whether and for how long anticoagulation is necessary after primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI).We aimed to study the impact of prolonged (>24 h) or brief (<24 h) postprocedural anticoagulation on infarct size assessed by cardiac magnetic resonance (CMR) after 30 days as well as on left ventricular ejection fraction (LVEF) and left ventricular (LV) remodeling evaluated by 2D-echocardiography after 9 months from the INNOVATION trial (Clinical Trial Registration: NCT02324348).Of the 114 patients (mean age: 59.5 years) enrolled, 76 (66.7%) received prolonged anticoagulation therapy (median duration: 72.6 h) and 38 (33.3%) patients received brief anticoagulation therapy (median duration: 5 h) after primary PCI. There was no significant difference in infarct size (mean size: 15.6% after prolonged anticoagulation versus 19.8% after brief anticoagulation, P = .100) and the incidence of microvascular obstruction (50.7% versus 52.9%, P = .830) between the groups. Even after adjusting, prolonged anticoagulation therapy could not reduce larger infarct (defined as >75 percentile of infarct size; 19.7% versus 35.3%; adjusted odd ratio [OR]: 0.435; 95% confidence interval [CI]: 0.120-1.57; P = .204). Similar results were observed in subanalyses of major high-risk subgroups. Moreover, follow-up LVEF <35% (3.2% versus 7.4%; adjusted OR: 0.383; 95% CI: 0.051-2.884; P = .352) and LV remodeling (defined as >20% increase in LV end-diastolic volume; 37.1% versus 18.5%; adjusted OR: 2.249; 95% CI: 0.593-8.535; P = .234) were similar between groups.These data suggest that prolonged postprocedural anticoagulation may not provide much benefit after successful primary PCI in patients with STEMI. However, further studies are needed.


Visualizing carbene equilibria.
Reviewed herein are equilibria between halocarbenes and halocarbanions, carbenes and carbene complexes and carbenes and O-ylides. The transient species were visualized by laser flash photolysis coupled with UV-Visible spectroscopy. This methodology enabled the determination of equilibrium constants and the extraction of associated thermodynamic parameters. Parallel computational studies provided anticipated structures and energies for the transient species, as well as electronic absorption wavelengths and oscillator strengths.


Anti-plasmodium activity of angiotensin II and related synthetic peptides.
Plasmodium species are the causative agents of malaria, the most devastating insect-borne parasite of human populations. Finding and developing new drugs for malaria treatment and prevention is the goal of much research. Angiotensins I and II (ang I and ang II) and six synthetic related peptides designated Vaniceres 1-6 (VC1-VC6) were assayed in vivo and in vitro for their effects on the development of the avian parasite, Plasmodium gallinaceum. Ang II and VC5 injected into the thoraces of the insects reduced mean intensities of infection in the mosquito salivary glands by 88% and 76%, respectively. Although the mechanism(s) of action is not completely understood, we have demonstrated that these peptides disrupt selectively the P.gallinaceum cell membrane. Additionally, incubation in vitro of sporozoites with VC5 reduced the infectivity of the parasites to their vertebrate host. VC5 has no observable agonist effects on vertebrates, and this makes it a promising drug for malaria prevention and chemotherapy.


Evidence that catecholamines stimulate renal gluconeogenesis through an alpha 1-type of adrenoceptor.
1. Noradrenaline stimulates gluconeogenesis through an alpha-adrenoceptor in renal cortical tubule fragments from fed rats incubated with 5 mM-lactate. 2. The selective alpha 1-adrenoreceptor agonist methoxamine stimulated gluconeogenesis, but the selective alpha 2-adrenoceptor agonist clonidine was ineffective. 3. The selective alpha 1-adrenoceptor antagonist thymoxamine blocked the stimulatory effects on gluconeogenesis of noradrenaline and of oxymetazoline (a synthetic alpha-agonist). The selective alpha 2-adrenoceptor antagonist yohimbine was ineffective in this respect. 4. It is concluded that noradrenaline and oxymetazoline stimulate gluconeogenesis in rat kidney via an alpha 1-rather than an alpha 2-type of adrenoceptor.


Disseminated Cat Scratch Disease in Pediatric Patients in Hawai'i.
Cat scratch disease is known to be a generally benign, self-resolving illness associated with non-specific symptoms, including lymphadenopathy, fever, fatigue, anorexia, and headaches. However, it can also cause disseminated disease with a wide range of manifestations, including liver and spleen microabscesses, osteomyelitis, encephalitis, and uveitis. Eighteen pediatric cases of disseminated cat scratch disease at a single center in Hawai'i are described. This case series emphasizes the importance of disease recognition and use of appropriate diagnostic tools and disease management. The disease burden of pediatric patients with disseminated cat scratch disease in the state of Hawai'i has a high incidence and should be considered in pediatric patients with prolonged febrile illnesses.


Specific in vitro binding of radiolabeled antibodies to cell surface antigens: interaction of antihuman thymocyte globulin with human target cells.
We have developed a highly sensitive and reproducible in vitro method to measure the rate and amount of binding of radiolabeled antibodies to target cells. We reduced non-specific binding of the antibodies to the target cells approx. 92% by removing protein aggregates from the antibody solutions. Using a specially designed cup that simultaneously allows washing and collection of target cells, cell loss was eliminated. This method was used to study the in vitro binding properties of the IgG fraction of anti-human thymocyte globulin (ATG) to nucleated human cells and to cells of other species. We found the initial rapid uptake of labeled ATG-IgG slowed with prolonged incubation. Incubation temperature and ATG concentration increased the rate of uptake. Sequential absorption studies indicated that initial uptake was due to rapidly binding antibodies. After these antibodies were removed, the rate of binding for antibodies that remained was several fold less than that of the antibodies removed by the initial absorption. Since temperature and the concentration of antibody and target cells can be rigidly controlled, this in vitro model system is ideally suited to quantify optimal conditions and kinetics of antibody binding to cell membrane antigens. Furthermore, the binding properties of antibody subpopulations in an antiserum may be determined by this technique. The maximum antibody binding capacity of various cell types can also be measured using the technique with a precision of +/- 14% on replicate determinations.


c-fos gene and protein expression in pelvic endometriosis: a local marker of estrogen action.
Endometriosis is an estrogen-dependent disease, causing pelvic pain and infertility. c-fos is an early transcription factor that has been reported to be related to estradiol-dependent cell proliferation. The aim of the present study was to assess the c-fos gene and protein expression in pelvic endometriotic implants in comparison to normal endometrium from infertile women. An open, prospective and controlled study included 15 infertile women with endometriosis and 19 control infertile women. Endometrial and endometriotic biopsies were performed at the follicular phase and the samples were processed for RT-PCR and immunohistochemistry. ERalpha mRNA levels were similar in the endometriotic implants/eutopic endometrium from women with endometriosis and in normal tissue (P = 0.649). The aromatase gene, however, was not expressed in the eutopic endometrium from either control or endometriosis groups, and was only expressed in 50% of endometriotic implants (P = 0.044). c-fos gene expression was higher in endometriotic implants (1.32 +/- 0.13; P = 0.011) than in eutopic endometrium from patients with endometriosis (0.97 +/- 0.11) or from the control group (0.91 +/- 0.05). In addition, immunohistochemistry showed a more abundant distribution of c-Fos in the stroma of endometriotic tissue compared to eutopic endometrium. These data suggest that c-fos may play a role in the molecular mechanisms of estrogen action on the induction, promotion or progression of endometriosis.


Effect of pentoxifylline on GFR decline in CKD: a pilot, double-blind, randomized, placebo-controlled trial.
Pentoxifylline is a nonspecific phosphodiesterase inhibitor with anti-inflammatory properties. It reduces proteinuria in patients with glomerular disease, although its impact on glomerular filtration rate (GFR) is unknown. We hypothesized that pentoxifylline would slow the estimated GFR decrease in patients with chronic kidney disease at high risk of progression. Pilot randomized double-blind placebo-controlled trial. 40 outpatients with decreased GFR, hypertension, and proteinuria greater than 1 g/24 h currently treated with angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or the combination and followed up in a nephrology clinic at a tertiary medical care facility. Pentoxifylline, 400 mg twice daily, or matching placebo. Difference in rates of estimated GFR change during the 1-year study period between the 2 groups. Estimated GFR (4-variable Modification of Diet in Renal Disease Study equation) and proteinuria by 24-hour urine collection were assessed at baseline and 6 and 12 months after enrollment. Baseline characteristics were similar between the 2 groups. At 1 year, the mean estimated GFR decrease was significantly less in the pentoxifylline group than the placebo group (-1.2 +/- 7.0 versus -7.2 +/- 8.2 mL/min/1.73 m2/y; mean difference, -6.0 mL/min/1.73 m2/y; 95% confidence interval, -11.4 to -0.6; P = 0.03). For pentoxifylline-treated participants, the mean estimated GFR decrease during treatment was slower compared with the year before study enrollment (-9.6 +/- 11.9 mL/min/1.73 m2/y; mean difference, -8.4 mL/min/1.73 m2/y; 95% confidence interval, -14.8 to -2.1; P = 0.01). Proteinuria was not different between the pentoxifylline and placebo groups at baseline, 6 months, or 1 year. Small sample size and incomplete follow-up. Pentoxifylline may slow the estimated GFR decrease in high-risk patients. This may be independent of its antiproteinuric properties and warrants further investigation.


Reliability of Untrained and Experienced Raters on FEES: Rating Overall Residue is a Simple Task.
The purpose of this study was to investigate the reliability of residue ratings on Fiberoptic Endoscopic Evaluation of Swallowing (FEES). We also examined rating differences based on experience to determine if years of experience influenced residue ratings. A group of 44 raters watched 81 FEES videos representing a wide range of residue severities for thin liquid, applesauce, and cracker boluses. Raters were untrained on the rating scales and simply rated their overall impression of residue amount on a visual analog scale (VAS) and a five-point ordinal scale in a randomized fashion across two sessions. Intra-class correlation coefficients, kappa coefficients, and ANOVAs were used to analyze agreement and differences in ratings. Residue ratings on both the VAS and ordinal scales had acceptable inter- and intra-rater reliability. Inter-rater agreement was acceptable (ICC > 0.7) for all comparisons. Intra-rater agreement was excellent on the VAS scale (rc = 0.9) and good on the ordinal scale (k = 0.78). There was no significant difference between expert ratings and other raters based on years of experience for cracker ratings (p = 0.2119) and applesauce ratings (p = 0.2899), but there was a significant difference between clinicians on thin liquid ratings (p = 0.0005). Without any specific training, raters demonstrated high reliability when rating the overall amount of residue on FEES. Years of experience with FEES did not influence residue ratings, suggesting that expert ratings of overall residue amount are not unique or specialized. Rating the overall amount of residue on FEES appears to be a simple visual-perceptual task for puree and cracker boluses.


Diageo's 'Stop Out of Control Drinking' Campaign in Ireland: An Analysis.
It has been argued that the alcohol industry uses corporate social responsibility activities to influence policy and undermine public health, and that every opportunity should be taken to scrutinise such activities. This study analyses a controversial Diageo-funded 'responsible drinking' campaign ("Stop out of Control Drinking", or SOOCD) in Ireland. The study aims to identify how the campaign and its advisory board members frame and define (i) alcohol-related harms, and their causes, and (ii) possible solutions. Documentary analysis of SOOCD campaign material. This includes newspaper articles (n = 9), media interviews (n = 11), Facebook posts (n = 92), and Tweets (n = 340) produced by the campaign and by board members. All material was coded inductively, and a thematic analysis undertaken, with codes aggregated into sub-themes. The SOOCD campaign utilises vague or self-defined concepts of 'out of control' and 'moderate' drinking, tending to present alcohol problems as behavioural rather than health issues. These are also unquantified with respect to actual drinking levels. It emphasises alcohol-related antisocial behaviour among young people, particularly young women. In discussing solutions to alcohol-related problems, it focuses on public opinion rather than on scientific evidence, and on educational approaches and information provision, misrepresenting these as effective. "Moderate drinking" is presented as a behavioural issue ("negative drinking behaviours"), rather than as a health issue. The 'Stop Out of Control Drinking' campaign frames alcohol problems and solutions in ways unfavourable to public health, and closely reflects other Diageo Corporate Social Responsibility (CSR) activity, as well as alcohol and tobacco industry strategies more generally. This framing, and in particular the framing of alcohol harms as a behavioural issue, with the implication that consumption should be guided only by self-defined limits, may not have been recognised by all board members. It suggests a need for awareness-raising efforts among the public, third sector and policymakers about alcohol industry strategies.


A role for macroautophagy in protection against 4-hydroxytamoxifen-induced cell death and the development of antiestrogen resistance.
This study identifies macroautophagy as a key mechanism of cell survival in estrogen receptor-positive (ER+) breast cancer cells undergoing treatment with 4-hydroxytamoxifen (4-OHT). This selective ER modifier is an active metabolite of tamoxifen commonly used for the treatment of breast cancer. Our study provides the following key findings: (a) only 20% to 25% of breast cancer cells treated with 4-OHT in vitro die via caspase-dependent cell death; more typically, the antiestrogen-treated ER+ breast cancer cells express increased levels of macroautophagy and are viable; (b) 4-OHT-induced cell death, but not 4-OHT-induced macroautophagy, can be blocked by the pan-caspase inhibitor z-VAD-fmk, providing strong evidence that these two outcomes of antiestrogen treatment are not linked in an obligatory manner; (c) 4-OHT-resistant cells selected from ER+ breast cancer cells show an increased ability to undergo antiestrogen-induced macroautophagy without induction of caspase-dependent cell death; and (d) 4-OHT, when used in combination with inhibitors of autophagosome function, induces robust, caspase-dependent apoptosis of ER+, 4-OHT-resistant breast cancer cells. To our knowledge, these studies provide the first evidence that macroautophagy plays a critical role in the development of antiestrogen resistance. We propose that targeting autophagosome function will improve the efficacy of hormonal treatment of ER+ breast cancer.


Delusions in Patients with Alzheimer's Disease: A Multidimensional Approach.
In Alzheimer's disease (AD) patients with delusions, clinical outcomes and mortality result from a combination of psychological, biological, functional, and environmental factors. We determined the effect of delusions on mortality risk, clinical outcomes linked to comprehensive geriatric assessment (CGA), cognitive, depressive, and neuropsychiatric symptoms (NPS) in 380 consecutive AD patients with Mini-Mental State Examination, Clinical Dementia Rating scale, 15-item Geriatric Depression Scale, and Neuropsychiatric Inventory (NPI), assessing one-year mortality risk using the Multidimensional Prognostic Index (MPI). We included 121 AD patients with delusions (AD-D) and 259 AD patients without delusions (AD-noD). AD-D patients were significantly older, with higher age at onset and cognitive impairment, a more severe stage of dementia, and more depressive symptoms than AD-noD patients. Disease duration was slightly higher in AD-D patients than in those without delusions, although this difference was not statistically significant. At CGA, AD-D patients showed a higher grade of disability in basic and instrumental activities of daily living, and an increased risk of malnutrition and bedsores. The two groups of patients significantly differed in MPI score (AD-D: 0.65 versus AD-noD: 0.51, p < 0.0001) and MPI grade. AD-D patients showed also a significant higher score in NPI of the following NPS than AD-noD patients: hallucinations, agitation/aggression, depression mood, apathy, irritability/lability, aberrant motor activity, sleep disturbances, and eating disorders. Therefore, AD-D patients showed higher dementia severity, and higher impairment in cognitive and depressive symptoms, and several neuropsychiatric domains than AD-noD patients, and this appeared to be associated with higher multidimensional impairment and increased risk of mortality.


Carbonic Anhydrase Inhibitors. Synthesis of Topically Effective Intraocular Pressure Lowering Agents Derived from 5-(omega-Amino- alkylcarboxamido)-1,3,4-Thia- diazole-2-Sulfonamide.
Reaction of the acyl chlorides of phthalimido-glycine or phthalimido-beta-alanine with 5-amino-1,3,4-thiadiazole-2-sulfonamide afforded after hydrazinolysis and deprotection of the phthalimido group the corresponding 5-(omega-aminoalkylcarboxamido)-1,3,4-thiadiazole-2-sulfonamides. Reaction of 5-(beta-aminoethylcarboxamido)-1,3,4-thiadiazole-2-sulfonamide with sulfonyl halides or acyl halides afforded a series of compounds possessing beta-alkyl/arylsulfonyl/carbonylamidoethylcarboxamido moieties in the 5 position of the thiadiazole-2-sulfonamide ring. The new derivatives were efficient inhibitors of three carbonic anhydrase (CA) isozymes, CA I, II (cytosolic forms) and IV (membrane-bound form), but especially against CA II and CA IV (in nanomolar range), the two isozymes known to play an important role in aqueous humor secretion within the ciliary processes of the eye. Some of the synthesized inhibitors possessed good water solubility (as hydrochlorides or sodium salts) and were applied as 2% solutions directly into the eye of normotensive or glaucomatous albino rabbits. Very strong intraocular pressure (IOP) lowering was observed for many of them for prolonged periods of 1-2 h, and the active drug was detected in eye tissues and fluids indicating that the antiglaucoma effect is due to CA inhibition within the eye.


Neurotrophic factor control of adult SVZ neurogenesis.
Neurogenesis is the process by which cells divide, migrate, and subsequently differentiate into a neuronal phenotype. Significant rates of neurogenesis persist into adulthood in two brain regions, the subgranular zone (SGZ) of the dentate gyrus and the subventricular zone (SVZ) of the lateral ventricles. Cells of the SVZ divide and migrate via the rostral migratory stream (RMS) to the olfactory bulb (OB) where they differentiate into granule and periglomerular cells. With the discovery of large-scale neurogenesis in the adult brain, there have been significant efforts to identify the mechanisms that control this process as well as the role of these cells in neuronal functioning. Neurotrophic factors are a family of molecules that serve critical roles in the survival and differentiation of neurons during development, as well as contribute to continued plasticity throughout life. Several members of the neurotrophin family have been implicated in the control of adult postnatal SVZ neurogenesis. In this review we will address what is currently known regarding neurotrophic factor-dependent control of SVZ neurogenesis and place these findings in the context of what is known regarding other growth factors.


17beta-estradiol, but not raloxifene, decreases thrombomodulin in the antithrombotic protein C pathway.
Raloxifene is a nonsteroidal selective estrogen receptor modulator (SERM) that mimics the effects of estrogen on some plasma lipids and may have direct effects on the vascular wall. The objective of this study was to determine the effects of 17beta-estradiol, raloxifene, and LY139,478 (a related benzothiophene SERM) on the anticoagulant protein C pathway. In human vascular endothelial cells activated with interleukin-1 (IL-1), we demonstrated decreased thrombomodulin-dependent protein C activation. 17beta-estradiol reduced the anticoagulant properties of both unstimulated and IL-1-activated endothelial cells by decreasing thrombomodulin expression. In contrast, raloxifene and LY139,478 enhanced the anticoagulant properties of both unstimulated and IL-1-activated endothelial cells through upregulation of thrombomodulin. Regulation of the protein C pathway via thrombomodulin on vascular endothelium may be a novel mechanism by which SERMs could potentially confer cardioprotective effects and reduce the thrombotic risk associated with HRT in compromised patients.


Prevalence and Correlates of Mental Health Problems in Norwegian Peacekeepers 18-38 Years Postdeployment.
Peacekeeping missions involve experiences that may impact the mental health of participating soldiers. However, research on the long-term mental health consequences of peacekeeping is sparse. The present study aimed to find the prevalence of mental health problems (MHPs), possible MHP predictors, and associations between predictors and MHPs in Norwegian peacekeepers 18-38 years after deployment to a United Nations peacekeeping mission. We used data from a cross-sectional, postdeployment survey of Norwegian peacekeepers who served in Lebanon between 1978 and 1998 (N = 10,605). Participants were assessed for posttraumatic stress disorder (PTSD); anxiety; depression; insomnia; alcohol misuse; drug misuse; and exposure to pre-, peri-, and postdeployment stressors. Logistic regressions were executed to explore key variables associated with MHPs. Total MHP prevalence was 15.1%, 95% CI [14.4, 15.8]. The estimates for specific disorders were 0.1% for drug misuse, 3.4% for alcohol misuse, 4.0% for depression, 6.2% for PTSD, 6.4% for anxiety, and 9.3% for insomnia. Postdeployment stressors, OR = 1.91, 95% CI [1.79, 2.04]; employment status, OR = 1.41, 95% CI [1.33, 1.48]; and traumatic exposure during deployment, OR = 1.11, 95% CI [1.09, 1.12], were positively related to PTSD, χ2(17, N = 8,568) = 1,791.299, p < .001. Similar patterns were found for the other MHPs. Considering that most participants (84.9%) reported low symptom levels, our findings challenge the widespread public perception that most peacekeepers have MHPs. Moreover, our results indicate that future peacekeepers should be prepared for challenges they may face not only during deployment but also in the years following their homecoming.


Beta-hydroxybutyrate dehydrogenase: lack in ruminant liver mitochondria.
The enizyme D(-)-beta-hydroxybutyrate dehydrogenase has been reported to occur in all mitochondria isolated from mammalian tissues and is especially high in liver. By contrast only very low concentration of the enzyme is detectable in mitachondria from bovine and sheep liver. The amount of the enzyme in mitochondria from other ruminant tissues such as kidney and heart are comparable with those from mammalian sources. The verv low activity of beta-hydroxybutyrate dehydrogenase is not referable to the iniability of substrates to penetrate milochondria or to decreased electron transfer activity but rather to a lack of the enzyne in ruminant liver mitochondria.


Direct comparison of the abilities of bone marrow mesenchymal versus hematopoietic stem cells to reverse hyperglycemia in diabetic NOD.SCID mice.
Both bone marrow-derived hematopoietic stem cells (HSC) and mesenchymal stem cells (MSC) improve glycemic control in diabetic mice, but their kinetics and associated changes in pancreatic morphology have not been directly compared. Our goal was to examine the time course of improvements in glucose tolerance and associated changes in β-cell mass and proliferation following transplantation of equivalent numbers of HSC or MSC from the same bone marrow into diabetic non-obese diabetic severe combined immune deficiency (NOD.SCID) mice. We used transgenic mice with a targeted expression of yellow fluorescent protein (YFP) driven by the Vav1 gene promoter to genetically tag HSC and progeny. HSC were separated from bone marrow by fluorescence-activated cell sorting and MSC following cell culture. Equivalent numbers of isolated HSC or MSC were transplanted directly into the pancreas of NOD.SCID mice previously made diabetic with streptozotocin. Glucose tolerance, serum insulin, β-cell mass and β-cell proliferation were examined up to 28 days following transplant. Transplantation with MSC improved glucose tolerance within 7 days and serum insulin levels increased, but with no increase in β-cell mass. Mice transplanted with HSC showed improved glucose tolerance only after 3 weeks associated with increased β-cell proliferation and mass. We conclude that single injections of either MSC or HSC transiently improved glycemic control in diabetic NOD.SCID mice, but with different time courses. However, only HSC infiltrated the islets and were associated with an expanded β-cell mass. This suggests that MSC and HSC have differing mechanisms of action.


Mast cell-derived histamine mediates cystitis pain.
Mast cells trigger inflammation that is associated with local pain, but the mechanisms mediating pain are unclear. Interstitial cystitis (IC) is a bladder disease that causes debilitating pelvic pain of unknown origin and without consistent inflammation, but IC symptoms correlate with elevated bladder lamina propria mast cell counts. We hypothesized that mast cells mediate pelvic pain directly and examined pain behavior using a murine model that recapitulates key aspects of IC. Infection of mice with pseudorabies virus (PRV) induces a neurogenic cystitis associated with lamina propria mast cell accumulation dependent upon tumor necrosis factor alpha (TNF), TNF-mediated bladder barrier dysfunction, and pelvic pain behavior, but the molecular basis for pelvic pain is unknown. In this study, both PRV-induced pelvic pain and bladder pathophysiology were abrogated in mast cell-deficient mice but were restored by reconstitution with wild type bone marrow. Pelvic pain developed normally in TNF- and TNF receptor-deficient mice, while bladder pathophysiology was abrogated. Conversely, genetic or pharmacologic disruption of histamine receptor H1R or H2R attenuated pelvic pain without altering pathophysiology. These data demonstrate that mast cells promote cystitis pain and bladder pathophysiology through the separable actions of histamine and TNF, respectively. Therefore, pain is independent of pathology and inflammation, and histamine receptors represent direct therapeutic targets for pain in IC and other chronic pain conditions.


Contrast adaptation and excitatory amino acid receptors in cat striate cortex.
We have employed two paradigms to investigate the mechanisms of contrast gain control in cat striate cortex. In the first paradigm, optimal drifting gratings were presented in three consecutive periods. The contrast was near threshold in the first and third periods and accompanied by iontophoretic pulses of glutamate or glutamate receptor (GluR) agonists. The contrast was set to evoke a higher firing rate in the second period. Although both visual and iontophoretic conditions were identical in the first and third periods, responses to glutamate, N-methyl-D-aspartic acid (NMDA), and (IS,3R)-1-Aminocyclopentane-1,3-dicarboxylic acid (ACPD) were reduced following the adapting interval. (S)-alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) responses were not reduced. Administration of ionotropic GluR antagonists did not affect adaptation to the high-contrast grating. The metabotropic GluR antagonist (+/-)-alpha-Methyl-4-carboxyphenylglycine (MCPG), which acts at presynaptic glutamate autoreceptors, decreased the degree of adaptation exhibited by striate cells. In a second paradigm, contrast response functions (CRFs) were obtained at various adapting contrasts and least-squares fits to a hyperbolic ratio equation generated for each adapting level. Similar to previous reports, DL-2-amino-5-phosphonovaleric acid (APV) reduced the slope of the CRF and increased the responsiveness of the cells but did not affect the semisaturation constant, sigma, or the exponent of the CRF, n. Only MCPG significantly altered the distribution of sigma and n for 19 cells. The effect on sigma suggests that this drug can interfere with the cell's ability to shift its operating point to match the adapting contrast. These results suggest the involvement of a presynaptic mechanism for contrast adaptation. The decrease in neuronal responsiveness immediately following the high-contrast period may reflect an additional, postsynaptic effect in which there is a decrease in the NMDA-mediated component of the visual response.


Purification and properties of D-myo-inositol 1,4,5-trisphosphate 3-kinase from bovine iris sphincter smooth muscle: effects of protein phosphorylation in vitro and in intact muscle.
Stimulation of bovine iris sphincter muscle with carbachol (10 microM) increased accumulation of Ins(1,4,5)P3 (InsP3) and Ins(1,3,4,5)P4 (InsP4) by 86 and 32% respectively. Addition of isoproterenol (5 microM) to muscle pretreated with carbachol reduced the 3H-radioactivity in InsP3 by 30% and increased that of InsP4 by 41%. InsP3 3-kinase was predominantly localized in the soluble fraction (110,000 g supernatant) of the iris sphincter. The enzyme was purified from this fraction by sequential chromatography on DEAE-cellulose, calmodulin (CAM)-agarose affinity, and Mono-Q anion-exchange columns. The specific activity of the purified enzyme was 1.94 mumol/min per mg protein with a purification of 114-fold, compared with the cytosolic fraction of the muscle. SDS/PAGE showed the enzyme to be associated with a protein band corresponding to 50 kDa. In the presence of 10 microM Ca2+, CaM dose-dependently stimulated the enzyme. InsP3 3-kinase specifically phosphorylated InsP3 with an apparent K(m) of 0.56 microM and a Vmax. of 2.5 mumol/min per mg protein. The stimulatory effect of CaM was due to a change in Vmax. and not in its K(m). The enzyme was maximally active at pH 7.0-7.5. Phosphorylation of the purified InsP3 3-kinase with protein kinase A increased its activity; in contrast, phosphorylation with protein kinase C inhibited the enzyme activity. Treatment of the intact iris sphincter with isoproterenol or phorbol 12,13-dibutyrate resulted in stimulation of InsP3 3-kinase activity in the soluble fraction and this activation was preserved on SDS/PAGE and renaturation. These results indicate that the bovine iris sphincter contains a Ca-CaM-dependent InsP3 3-kinase which can be differentially regulated, both in vitro and in intact muscle, by protein kinases A and C.


What proportion of patients with chronic noncancer pain are prescribed an opioid medicine? Systematic review and meta-regression of observational studies.
Guidelines now discourage opioid analgesics for chronic noncancer pain because the benefits frequently do not outweigh the harms. We aimed to determine the proportion of patients with chronic noncancer pain who are prescribed an opioid, the types prescribed and factors associated with prescribing. Database searches were conducted from inception to 29 October 2018 without language restrictions. We included observational studies of adults with chronic noncancer pain measuring opioid prescribing. Opioids were categorized as weak (e.g. codeine) or strong (e.g. oxycodone). Study quality was assessed using a risk of bias tool designed for observational studies measuring prevalence. Individual study results were pooled using a random-effects model. Meta-regression investigated study-level factors associated with prescribing (e.g. sampling year, geographic region as per World Health Organization). The overall evidence quality was assessed using Grading of Recommendations Assessment, Development and Evaluation criteria. Of the 42 studies (5,059,098 participants) identified, the majority (n = 28) were from the United States of America. Eleven studies were at low risk of bias. The pooled estimate of the proportion of patients with chronic noncancer pain prescribed opioids was 30.7% (95% CI 28.7% to 32.7%, n = 42 studies, moderate-quality evidence). Strong opioids were more frequently prescribed than weak (18.4% (95% CI 16.0-21.0%, n = 15 studies, low-quality evidence), versus 8.5% (95% CI 7.2-9.9%, n = 15 studies, low-quality evidence)). Meta-regression determined that opioid prescribing was associated with year of sampling (more prescribing in recent years) (P = 0.014) and not geographic region (P = 0.056). Opioid prescribing for patients with chronic noncancer pain is common and has increased over time.


Human Movement Recognition Based on 3D Point Cloud Spatiotemporal Information from Millimeter-Wave Radar.
Human movement recognition is the use of perceptual technology to collect some of the limb or body movements presented. This practice involves the use of wireless signals, processing, and classification to identify some of the regular movements of the human body. It has a wide range of application prospects, including in intelligent pensions, remote health monitoring, and child supervision. Among the traditional human movement recognition methods, the widely used ones are video image-based recognition technology and Wi-Fi-based recognition technology. However, in some dim and imperfect weather environments, it is not easy to maintain a high performance and recognition rate for human movement recognition using video images. There is the problem of a low recognition degree for Wi-Fi recognition of human movement in the case of a complex environment. Most of the previous research on human movement recognition is based on LiDAR perception technology. LiDAR scanning using a three-dimensional static point cloud can only present the point cloud characteristics of static objects; it struggles to reflect all the characteristics of moving objects. In addition, due to its consideration of privacy and security issues, the dynamic millimeter-wave radar point cloud used in the previous study on the existing problems of human body movement recognition performance is better, with the recognition of human movement characteristics in non-line-of-sight situations as well as better protection of people's privacy. In this paper, we propose a human motion feature recognition system (PNHM) based on spatiotemporal information of the 3D point cloud of millimeter-wave radar, design a neural network based on the network PointNet++ in order to effectively recognize human motion features, and study four human motions based on the threshold method. The data set of the four movements of the human body at two angles in two experimental environments was constructed. This paper compares four standard mainstream 3D point cloud human action recognition models for the system. The experimental results show that the recognition accuracy of the human body's when walking upright can reach 94%, the recognition accuracy when moving from squatting to standing can reach 84%, that when moving from standing to sitting can reach 87%, and the recognition accuracy of falling can reach 93%.


Prevalence of work-related musculoskeletal disorders among hairdressers.
This study has investigated the prevalence of work-related musculoskeletal disorders (WMSDs), the most commonly affected body parts, the risk factors of WMSDs and the coping strategies adopted by hairdressers. The study design was a cross-sectional descriptive survey design. Two hundred and ninety-nine hairdressers (242 females and 57 males) from salons in Surulere and Mushin Local Government Areas of Lagos State completed a 27-item questionnaire. They were selected using a non-probability consecutive sampling technique. The inferential analysis was conducted using the Chi2 test. The level of significance stood at p < 0.05. The 12-month prevalence of musculoskeletal disorders stood at 75.6%. Two hundred and twenty-one (91.3%) participants reported gradual onset of musculoskeletal disorders. One hundred and sixteen (47.9%) participants had the onset of the WMSDs at the age range of 26-35 years. The most commonly affected body parts included the low back (76.3%), shoulder (62.5%) and neck (46.3%). Some of the major job risk factors of the WMSDs that were identified included: working in the same position for long periods and attending to a large number of customers in 1 day. Taking sufficient rest breaks by participants was one of the coping strategies adopted by the participants. The mean number of years of working experience was 7.85±0.4 years. One hundred and twenty-four (41.5%) participants had worked for 1-5 years. The Chi2 analysis showed that the prevalence of musculoskeletal disorders were significantly associated with the age of a participant (Chi2 = 78.78, p = 0.001), years of working experience (Chi2 = 78.03, p = 0.001) and hours spent working in a standing position (Chi2 = 8.77, p = 0.01), respectively. The age of hairdressers, their years of working and the long hours they spent working in a standing position may be significant factors that contribute to the high prevalence of the WMSDs among them. The most commonly affected body parts included the low back, shoulders and neck.


Correlation between Reflux and multichannel intraluminal impedance pH monitoring in untreated volunteers.
Although probable causative agents have been identified (e.g., refluxate components, tobacco smoke), the definitive mechanism for inflammation-related laryngeal mucosal damage remains elusive. Multichannel intraluminal impedance combined with pH monitoring (MII/pH) has emerged as a sensitive tool for diagnosis and characterization of gastroesophageal reflux disease with laryngopharyngeal manifestations. To determine the relationship between laryngeal signs and MII/pH, we examined correlations between Reflux Finding Score (RFS) ratings of videostroboscopic laryngeal examinations and findings from MII/pH. Correlational study. Healthy, untreated volunteers (n = 142) underwent reflux diagnosis using data acquired from MII/pH testing. Eight trained clinicians performed RFS ratings of corresponding laryngeal examinations. Averaged RFS ratings were compared to MII/pH data using Pearson correlation coefficients. The relationship between RFS and MII/pH findings and demographic/clinical information (age, sex, smoking status, reflux) was assessed using general linear modeling. Rater reliability was evaluated. Posterior commissure hypertrophy was negatively correlated with minutes of nonacid refluxate (R = -0.21, P = .0115). General linear modeling revealed that 28% to 40% of the variance in ratings of ventricular obliteration, erythema/hyperemia, vocal fold edema, diffuse laryngeal edema, posterior commissure hypertrophy, and granulation/granuloma could be explained by main and interaction effects of age, sex, smoking status, and reflux. Intra- and inter-rater reliability for RFS were poor-fair. These results support the theory that the RFS is not specific for reflux in healthy, untreated volunteers, suggesting there may be alternate explanations for inflammatory clinical signs commonly ascribed to reflux in this population.


Simulated pediatric cardiopulmonary resuscitation: initial events and response times of a hospital arrest team.
Cardiopulmonary resuscitation (CPR) training programs exist to enhance knowledge and skills retention. However, they do not ensure that effective CPR will be performed by trainees or resuscitation teams. One aspect of CPR effectiveness is the ability of the team to respond to an emergency call in a timely manner. We prospectively evaluated the time required for team members to respond to an emergency call and to initiate definitive treatment in our pediatric facility. The medical staff who responded had no prior knowledge of the simulated cardiac arrest (SCA) events. All events were recorded on audio-cassette tape to determine the sequence of events and response time of arrest team members. SCA scenarios represented examples of cardiac, hematologic, renal, respiratory, and pharmacologic pathophysiology. All participants were instructed to respond as though the SCA were an actual emergency. From December 1991 to January 1993, 37 SCAs were evaluated. Documentation began after a concise arrest scenario had been presented to a designated nursing representative who was to be the first rescuer on the scene. The rescuer first assessed the patient's condition, activated the cardiac arrest system (median elapsed time, MET, 0.50 minutes), and then initiated single-person CPR (MET 0.58 minutes). Administration of oxygen occurred at an MET of 2.25 minutes. The first member of the arrest team to respond was the pediatric resident (MET 3.17 minutes) followed by the respiratory therapist (MET 3.20 minutes), an ICU nurse (MET 3.58 minutes), a pharmacist (MET 3.42 minutes), and anesthesiology personnel (MET 4.70 minutes). The use of SCAs (termed "Mega Code") serves as an extension of Basic Life Support and Advanced Cardiac Life Support education and provides a valuable learning experience and quality assurance tool. Limitations that might influence patient outcome during an actual in-hospital arrest have led to refinements in our cardiac arrest procedures. Of particular note was the delay in oxygen administration, which may be linked to its omission from the 1986 and 1992 American Heart Association Basic Life Support Guidelines. We believe that BLS education for hospital employees should include and emphasize oxygen delivery for resuscitation.


Design, synthesis, and biological evaluation of 2-amino-6-methyl-phenol derivatives targeting lipid peroxidation with potent anti-ferroptotic activities.
The suppression of ferroptosis is emerging as a promising therapeutic strategy for effectively treating a wide range of diseases, including neurodegenerative disorders, organ ischemia-reperfusion injury, and inflammatory conditions. However, the clinical utility of ferroptosis inhibitors is significantly impeded by the limited availability of rational drug designs. In our previous study, we successfully unraveled the efficacy of ferrostatin-1 (Fer-1) attributed to the synergistic effect of its ortho-diamine (-NH) moiety. In this study, we present the discovery of the ortho-hydroxyl-amino moiety as a novel scaffold for ferroptosis inhibitors, employing quantum chemistry as well as in vitro and in vivo assays. 2-amino-6-methylphenol derivatives demonstrated remarkable inhibition of RSL3-induced ferroptosis, exhibiting EC50 values ranging from 25 nM to 207 nM. These compounds do not appear to modulate iron homeostasis or lipid reactive oxygen species (ROS) generation pathways. Nevertheless, they effectively prevent the accumulation of lipid peroxides in living cells. Furthermore, compound 13 exhibits good in vivo activities as it effectively protect mice from kidney ischemia-reperfusion injury. In summary, compound 13 has been identified as a potent ferroptosis inhibitor, warranting further investigation as a promising lead compound.


The impact of hypercarbia on the evolution of brain injury in a porcine model of traumatic brain injury and systemic hemorrhage.
Carbon dioxide is perhaps the most potent available modulator of cerebrovascular tone and thus cerebral blood flow (CBF). These experiments evaluate the impact of induced hypercarbia on the matching of blood flow and metabolism in the injured brain. We explore the hypothesis that hypercarbia will restore the relationship of CBF to metabolic demand, resulting in improved outcome following traumatic brain injury (TBI) and hemorrhage. A behavioral outcome score, hemodynamic, metabolic, and pathologic parameters were assessed in anesthetized and ventilated juvenile pigs. Animals were assigned to either normocarbia or hypercarbia and subdivided into TBI (via fluid percussion) with or without hemorrhage. The experimental groups were TBI; TBI + 40% hemorrhage (40%H); TBI + hypercarbia (CO2); and TBI + 40%H + CO2. Hemorrhaged animals were resuscitated with blood and crystalloid. Hypercarbia was induced immediately following TBI using 10% FiCO2. The normocarbic group demonstrated disturbance of the matching of CBF to metabolism evidenced by statistically significant increases in cerebral oxygen and glucose extraction. Hypercarbic animals showed falls in the same parameters, demonstrating improvement in the matching of CBF to metabolic demand. Parenchymal injury was significantly decreased in hypercarbic animals: 3/10 hypercarbic versus 6/8 normocarbic animals showed cerebral contusions at the gray/white interface (p = 0.05). The hypercarbic group had significantly better behavioral outcome scores, 10.5, versus 7.3 for the normocarbic groups (p = 0.005). The decreased incidence of cerebral contusion and improved behavioral outcome scores in our experiments appear to be mediated by better matching of cerebral metabolism and blood flow, suggesting that manipulations modulating the balance of blood flow and metabolism in injured brain may improve outcomes from TBI.


Effect of Dentin Moisture in Posterior Restorations Performed with Universal Adhesive: A Randomized Clinical Trial.
This double-blind, randomized clinical trial evaluated the influence of dentin moisture on postoperative sensitivity (POS), as well as, on clinical performance in posterior bulk-fill composite restorations, using a universal adhesive, until 12 months after clinical service. In accordance with a split-mouth design, 45 patients received posterior restorations, restored with a bulk-fill resin composite (Filtek Bulk Fill, 3M Oral Care) and a universal adhesive used in etch-and-rinse mode (SBU; Single Bond Universal Adhesive), which were applied on dry or moist dentin, with a cavity depth of at least 3 mm. Three operators placed 90 Class I/Class II restorations. Patients were evaluated for spontaneous and stimulated POS in the baseline, and after 48 hours, 7 days, and at 6 and 12 months. In addition, secondary parameters (marginal discoloration, marginal adaptation, fracture, and recurrent caries) were evaluated by World Dental Federation (FDI) criteria after 7 days and at 6 and 12 months. Statistical analyzes were performed using the Chi-square, Fisher exact, Friedman, Kruskall-Wallis, and Mann-Whitney tests (α=0.05). No significant spontaneous and stimulated POS was observed when SBU was applied in dry and moist dentin (p>0.05). A significant and higher risk of spontaneous POS (20.0%; 95%CI 10.9-33.82 for dry dentin and 22.22%; 95%CI 12.54-36.27 for moist dentin) occurred up to 48 hours after restoration placement for the dry and moist dentin groups (p<0.02). However, the POS intensity was mild up to 48 hours with no significant difference between dry and moist dentin groups (p>0.79). When secondary parameters were evaluated, no significant differences between the groups were observed. Dentin moisture did not influence POS in posterior bulk-fill composite restorations when associated with a universal adhesive applied in etch-and-rinse mode.


Critical energies for ssb and dsb induction in plasmid DNA by vacuum-UV photons: an arrangement for irradiating dry or hydrated DNA with monochromatic photons.
Theoretical modelling techniques are often used to simulate the action of ionizing radiations on cells at the nanometre level. Using monoenergetic vacuum-UV (VUV) radiation to irradiate DNA either dry or humidified, the action spectra for the induction of DNA damage by low energy photons and the role of water and can be studied. These data provide inputs for the theoretical models. Various combinations of monochromator, grating and VUV window have been used to obtain monochromatic photons from the 2 GeV electron synchrotron at the CLRC, Daresbury Laboratory. A sample chamber containing plasmid DNA is installed at the end of the beamline. The chamber can be evacuated or water can be introduced (as water vapour or humidified helium). In this way, DNA can be irradiated either dry or humidified. An arrangement for irradiating dry or humidified DNA using monoenergetic photons from 7 eV to 150 eV has been developed. At the energies used, exposure rates vary from about 5 x 10(10) to 3 x 10(12) photons cm(-2) s(-1) over a 1 cm2 sample area. At all but the lowest energies this is sufficient to produce significant levels of DNA damage in just a few minutes. The measured dose variation over the sample area is typically 30%, but this is reduced significantly using sample scanning techniques.


Reproducible methods for calibrating the backscattered electron signal for quantitative assessment of mineral content in bone.
Backscattered electron (BSE) imaging shows promise for orthopaedic and bone research. BSE images of bone may be captured on-line directly from the scanning electron microscope (SEM), and then analyzed to produce a backscattered electron profile (BSEP), a modified image graylevel histogram which is representative of the mineral content in bone. The goals of this work were 1) develop a reproducible graylevel calibration technique for bone specimens, and 2) determine a conservative time interval during which SEM operating conditions would remain stable. Calibration standards containing pure aluminum and pure magnesium wires were placed in the SEM with human cancellous bone. Baseline imaging conditions were first established by adjusting the SEM until the bone image displayed good resolution and graylevel separation between regions of different mineral content. Microscope brightness and contrast controls were randomly changed to initiate the new operating conditions of another imaging session, and graylevel values from the calibration metals were used to readjust the microscope back to baseline operating conditions. Weighted mean graylevel values of the BSEPs from calibration trials were compared to those of the baseline. Data showed that bone images could be reproduced within 1.2 percent. It was also concluded that our equipment required calibration checks at 20 minute intervals.


Applicability of Generic Assays Based on Liquid Chromatography-Electrospray Mass Spectrometry to Study in vitro Metabolism of 55 Structurally Diverse Compounds.
Liquid chromatography-mass spectrometry (LC-MS) with generic gradient elution for a large number of chemically different compounds is a common approach in drug development, used to acquire a large amount of data in a short time frame for drug candidates. The analysis with non-optimized parameters however may lead to a poor method performance for many compounds, and contains a risk of losing important information. Here, generic electrospray time of flight (ESI-TOF) MS methods in various pH conditions were tested for 55 chemically diverse compounds (10 acids, 25 bases, 17 neutrals, and 3 amphoterics), aiming to find best analytical conditions for each compound, for studies of in vitro metabolic properties in liver preparations. The effect of eluent pH and elution gradient strength on chromatographic performance and electrospray MS ionization efficiency were examined for each compound. The data are evaluated how well the best generic approach could cover the analysis of test compounds and how many compounds would still need completely different analytical conditions after that. Aqueous mobile phase consisting of 0.05% acetic acid and 5 mM ammonium acetate (pH 4.4) showed the best general suitability for the analyses, showing adequate performance for metabolite profiling for 41 out of 55 compounds either in positive or negative ion mode. In positive ion mode, the main limitation of performance in various pH conditions was generally not the lack of ionization, but rather the poor chromatographic performance (inadequate retention or poor peak shape), suggesting that more emphasis should be put in finding conditions providing best chromatographic performance, rather than highest ionization properties. However, a single generic approach for a large number of different compounds is not likely to produce good results for all compounds. Preferably, at least two or three different conditions are needed for the coverage of a larger number of structurally diverse compounds.


Adverse postoperative outcomes in surgical patients with immune thrombocytopenia.
Patients with immune thrombocytopenia (ITP) are likely to have various medical co-morbidities, yet their global features regarding adverse postoperative outcomes and use of medical resources when undergoing major surgery are unknown. The objective of this study was to validate whether ITP is an independent risk factor for adverse postoperative outcomes, and to explore the potential clinical predictors of outcomes after major surgery among patients with ITP. A retrospective population-based cohort study was conducted using Taiwan's National Health Insurance Research Database, controlling for preoperative co-morbidities by means of multiple logistic regression. Major postoperative complication and mortality rates, and in-hospital medical costs were analysed. The study included 11,085 surgical patients with ITP and 44,340 controls without ITP matched for sex, age, and type of surgery and anaesthesia. Surgical patients with ITP had a higher risk of postoperative death (odds ratio (OR) 1.89, 95 per cent confidence interval 1.57 to 2.27), and overall postoperative complications (OR 1.47, 1.39 to 1.56), and increased hospital stay (OR 1.90, 1.80 to 2.01), admission to the intensive care unit (OR 1.73, 1.63 to 1.83) and medical costs (OR 1.89, 1.79 to 1.99). Amount of preoperative platelet and/or red blood cell transfusion, emergency visits and admission to hospital for ITP care were identified as risk factors for adverse postoperative outcomes. Patients with ITP undergoing surgery are at increased risk of adverse perioperative events, particularly if blood or blood product transfusion are required preoperatively, or the procedure is done as an emergency.


[Nephroblastoma in children. Results of treatment (1989-1994)].
The experience of combined treatment of 75 children with nephroblastoma (1989-1994) has been evaluated. A relationship between the treatment results, on the one hand, and stage and histological pattern of tumor, on the other, has been established. The analysis confirmed the following progress made during 1973-1988 and 1989-1994: 2-year recurrence-free survival increased from 38.9 to 79.4% while 5-year survival--from 35.2 to 72.6%.


Effects of Different Levels of Calcium Intake on Brain Cell Apoptosis in Fluorosis Rat Offspring and Its Molecular Mechanism.
The purpose of the investigation is to reveal the influence of dietary calcium on fluorosis-induced brain cell apoptosis in rat offspring, as well as the underlying molecular mechanism. Sprague-Dawley (SD) female rats were randomly divided into five groups: control group, fluoride group, low calcium, low calcium fluoride group, and high calcium fluoride group. SD male rats were used for breeding only. After 3 months, male and female rats were mated in a 1:1 ratio. Subsequently, 18-day-old gestation rats and 14- and 28-day-old rats were used as experimental subjects. We determined the blood/urine fluoride, the blood/urine calcium, the apoptosis in the hippocampus, and the expression levels of apoptosis-related genes, namely Bcl-2, caspase 12, and JNK. Blood or blood/urine fluoride levels and apoptotic cells were found significantly increased in fluorosis rat offspring as compared to controls. Furthermore, the Bcl-2 messenger RNA (mRNA) expression levels significantly decreased, and caspase 12 mRNA levels significantly increased in each age group as compared to controls. Compared with the fluoride group, the blood/urine fluoride content and apoptotic cells evidently decreased in the high calcium fluoride group, Bcl-2 mRNA expression significantly increased and caspase 12 mRNA expression significantly decreased in each age group. All results showed no gender difference. Based on these results, the molecular mechanisms of fluorosis-induced brain cell apoptosis in rat offspring may include the decrease in Bcl-2 mRNA expression level and increase in caspase 12 mRNA expression signaling pathways. High calcium intake could reverse these gene expression trends. By contrast, low calcium intake intensified the toxic effects of fluoride on brain cells.


[Treatment policy for children with complicated osteoarticular tuberculosis].
Experience in treating 97 children aged 1 to 14 years who had complicated tuberculosis of the spine (n = 74) and large joints (n = 23) in a specialized surgical clinical setting is presented. The developed treatment policy involves early radical reparative or reconstructive surgical intervention and intensive long-term therapy. The treatment allows one to cure 96.3% of children, yielding good functional results in 82.5% of them.


Clinical importance of aspirin and clopidogrel resistance.
Aspirin and clopidogrel are important components of medical therapy for patients with acute coronary syndromes, for those who received coronary artery stents and in the secondary prevention of ischaemic stroke. Despite their use, a significant number of patients experience recurrent adverse ischaemic events. Interindividual variability of platelet aggregation in response to these antiplatelet agents may be an explanation for some of these recurrent events, and small trials have linked "aspirin and/or clopidogrel resistance", as measured by platelet function tests, to adverse events. We systematically reviewed all available evidence on the prevalence of aspirin/clopidogrel resistance, their possible risk factors and their association with clinical outcomes. We also identified articles showing possible treatments. After analyzing the data on different laboratory methods, we found that aspirin/clopidogrel resistance seems to be associated with poor clinical outcomes and there is currently no standardized or widely accepted definition of clopidogrel resistance. Therefore, we conclude that specific treatment recommendations are not established for patients who exhibit high platelet reactivity during aspirin/clopidogrel therapy or who have poor platelet inhibition by clopidogrel.


Circulating muramyl dipeptide is negatively associated with interleukin-10 in the frail elderly.
Elevated levels of serum cytokines, a marker of immune activation and chronic inflammation, are commonly associated with age and are a significant risk factor for all-cause mortality in the elderly. This phenomenon is very similar to that exhibited by individuals with diseases of inflammatory etiology and chronic viral infections such as human immunodeficiency virus (HIV). Although the origin of chronically elevated cytokines with age is unknown, for chronic diseases and viral infections, a role for circulating bacterial products and other pattern recognition receptor (PRR) ligands has been suggested. Given this, we sought to examine whether the levels of circulating cytokines (tumour necrosis factor (TNF), interferon-gamma (IFN-γ), interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-12) in the advanced-age, frail elderly (n = 135) correlated with plasma levels of lipopolysaccharide (LPS), muramyl dipeptide (MDP), 16S ribosomal DNA, total cell-free DNA and host-derived mitochondrial DNA. After adjusting for multiple testing, no associations between circulating products and donor age, sex or comorbidities were observed. However, a significant negative correlation between MDP and IL-10 was identified. Given the anti-inflammatory nature of IL-10, a negative relationship with a potent inflammatory agonist such as MDP is not surprising and suggests a potential role for circulating MDP in the propagation of age-related immune activation.


Prevalence and factors associated with changes in frailty among community-dwelling older adults in Japan during the COVID-19 pandemic: A prospective cohort study from 2020 to 2022.
This study aimed to ascertain the prevalence of frailty during the pandemic and to determine factors associated with changes in frailty status. In May-June of 2020-2022, we assessed the frailty of 549 participants using the Kihon Checklist. Furthermore, we classified participant residences as urban, suburban, and rural and investigated participants' engagement in hobbies and community activities in 2020 and 2022. Cochran's Q test was used to analyze the proportions of frailty status. Subsequently, we conducted a binomial logistic regression analysis with the improvement/deterioration of frailty status from 2020 to 2022 as the dependent variable, and engagement in hobbies and community activities as the independent variables. Significant changes were observed among participants in urban areas, where an increase in pre-frailty and a decrease in robust individuals from 2020 to 2021 were noted. Focusing on item no. 17 (going out), the decreasing frequency had recovered by 2022 in the group of all groups. Continued engagement in only hobbies or only community activities, and continued engagement in both were associated with remained robust/frailty-status improvement. Moreover, not engaging in either hobbies or community activities was associated with remained frail/frailty-status deterioration. During the early stages, the COVID-19 pandemic impacted the frailty of older adults in densely populated areas. The results also suggest an attenuation in the decline in older adult activity in 2022. Continuous engagement in hobbies and community activities was crucial for improving and preventing deterioration in frailty status during the COVID-19 pandemic. Geriatr Gerontol Int 2023; ••: ••-••.


The influence of passive stretch and NF-κB inhibitors on the morphology of dystrophic muscle fibers.
The triangularis sterni (TS) is an expiratory muscle that is passively stretched during inspiration. The magnitude of passive stretch depends upon the location of individual fibers within the TS muscle, with fibers located more caudally being stretched ∼ 5% to 10% more than fibers in the cephalad region. In the mdx mouse model for muscular dystrophy, the TS exhibits severe pathological alterations that are ameliorated by treatment with inhibitors of the NF-κB pathway. The purpose of this study was to assess the influence of passive stretch in vivo on fiber morphology in nondystrophic and mdx TS muscles, and the morphological benefits of treating mdx mice with two distinct NF-κB inhibitors, pyrrolidine dithiocarbamate (PDTC), and ursodeoxycholic acid (UDCA). Transmission electron microscopy revealed Z-line streaming, hypercontraction, and disassociation of the plasma membrane from the basal lamina in mdx fibers. In both nondystrophic and mdx TS muscles, fiber density was larger in more caudal regions. In comparison with nondystrophic TS, fibers in the mdx TS exhibited substantial reductions in diameter throughout all regions. In vivo treatment with either PDTC or UDCA tended to increase fiber diameter in the middle and decrease fiber diameter in the caudal TS, while reducing centronucleation in the middle region. These results suggest that passive stretch induces hypercontraction and plasma membrane abnormalities in dystrophic muscle, and that differences in the magnitude of passive stretch may influence fiber morphology and the actions of NF-κB inhibitors on dystrophic morphology.


Antimicrobial and Antibiofilm Effects of Human Amniotic/Chorionic Membrane Extract on Streptococcus pneumoniae.
Background:Streptococcus pneumoniae colonize the human nasopharynx in the form of biofilms. The biofilms act as bacterial reservoirs and planktonic bacteria from these biofilms can migrate to other sterile anatomical sites to cause pneumonia, otitis media (OM), bacteremia and meningitis. Human amniotic membrane contains numerous growth factors and antimicrobial activity; however, these have not been studied in detail. In this study, we prepared amniotic membrane extract and chorionic membrane extract (AME/CME) and evaluated their antibacterial and antibiofilm activities against S. pneumoniae using an in vitro biofilm model and in vivo OM rat model. Materials and Methods: The AME/CME were prepared and protein was quantified using DCTM (detergent compatible) method. The minimum inhibitory concentrations were determined using broth dilution method, and the synergistic effect of AME/CME with Penicillin-streptomycin was detected checkerboard. The in vitro biofilm and in vivo colonization of S. pneumoniae were studied using microtiter plate assay and OM rat model, respectively. The AME/CME-treated biofilms were examined using scanning electron microscope and confocal microscopy. To examine the constituents of AME/CME, we determined the proteins and peptides of AME/CME using tandem mass tag-based quantitative mass spectrometry. Results: AME/CME treatment significantly (p < 0.05) inhibited S. pneumoniae growth in planktonic form and in biofilms. Combined application of AME/CME and Penicillin-streptomycin solution had a synergistic effect against S. pneumoniae. Biofilms grown with AME/CME were thin, scattered, and unorganized. AME/CME effectively eradicated pre-established pneumococci biofilms and has a bactericidal effect. AME treatment significantly (p < 0.05) reduced bacterial colonization in the rat middle ear. The proteomics analysis revealed that the AME/CME contains hydrolase, ribonuclease, protease, and other antimicrobial proteins and peptides. Conclusion: AME/CME inhibits S. pneumoniae growth in the planktonic and biofilm states via its antimicrobial proteins and peptides. AME/CME are non-cytotoxic, natural human product; therefore, they may be used alone or with antibiotics to treat S. pneumoniae infections.


Reconstructing the value puzzle in health technology assessment: a pragmatic review to determine which modelling methods can account for additional value elements.
Health technology assessment (HTA) has traditionally relied on cost-effectiveness analysis (CEA) as a cornerstone of evaluation of new therapies, assessing the clinical validity and utility, the efficacy, and the cost-effectiveness of new interventions. The current format of cost-effectiveness analysis, however, does not allow for inclusion of more holistic aspects of health and, therefore, value elements for new technologies such as the impact on patients and society beyond its pure clinical and economic value. This study aimed to review the recent modelling attempts to expand the traditional cost-effectiveness analysis approach by incorporating additional elements of value in health technology assessment. A pragmatic literature review was conducted for articles published between 2012 and 2022 reporting cost-effectiveness analysis including value aspects beyond the clinical and cost-effectiveness estimates; searches identified 13 articles that were eligible for inclusion. These expanded modelling approaches mainly focused on integrating the impact of societal values and health equity in cost-effectiveness analysis, both of which were championed as important aspects of health technology assessment that should be incorporated into future technology assessments. The reviewed cost-effectiveness analysis methods included modification of the current cost-effectiveness analysis methodology (distributional cost-effectiveness analysis, augmented cost-effectiveness analysis, extended cost-effectiveness analysis) or the use of multi-criteria decision analysis. Of these approaches, augmented cost-effectiveness analysis appears to have the most potential by expanding traditional aspects of value, as it uses techniques already familiar to health technology assessment agencies but also allows space for incorporation of qualitative aspects of a product's value. This review showcases that methods to unravel additional value elements for technology assessment exist, therefore, patient access to promising technologies can be improved by moving the discussion from "if" to "how" additional value elements can inform decision-making.


Rates of disease progression according to initial highly active antiretroviral therapy regimen: a collaborative analysis of 12 prospective cohort studies.
No large clinical end-point trials have been conducted comparing regimens among human immunodeficiency virus type 1-positive persons starting antiretroviral therapy. We examined clinical progression according to initial regimen in the Antiretroviral Therapy Cohort Collaboration, which is based on 12 European and North American cohort studies. We analyzed progression to death from any cause and to AIDS or death (AIDS/death), comparing efavirenz (EFV), nevirapine (NVP), nelfinavir, idinavir, ritonavir (RTV), RTV-boosted protease inhibitors (PIs), saquinavir, and abacavir. We also compared nucleoside reverse-transcriptase inhibitor pairs: zidovudine/lamivudine (AZT/3TC), stavudine (D4T)/3TC, D4T/didanosine (DDI), and others. A total of 17,666 treatment-naive patients, 55,622 person-years at risk, 1,617 new AIDS events, and 895 deaths were analyzed. Compared with EFV, the adjusted hazard ratio (HR) for AIDS/death was 1.28 (95% confidence interval [CI], 1.03-1.60) for NVP, 1.31 (95% CI, 1.01-1.71) for RTV, and 1.45 (95% CI, 1.15-1.81) for RTV-boosted PIs. For death, the adjusted HR for NVP was 1.65 (95% CI, 1.16-2.36). The adjusted HR for death for D4T/3TC was 1.35 (95% CI, 1.14-1.59), compared with AZT/3TC. Outcomes may vary across initial regimens. Results are observational and may have been affected by bias due to unmeasured or residual confounding. There is a need for large, randomized, clinical end-point trials.


[Hepatotoxicity of valproic acid treatment].
Hepatotoxicity of valproic acid (VPA) is reported in a psychomotor retarded boy. A four-month antiepileptic therapy was followed by a combined VPA/phenytoin treatment where-upon, two months later, the patient died in a hepatic coma. In the final state the metabolic pattern of VPA was still found within the normal range with the exception of the two abnormal metabolites 4-en-VPA) (2-propyl-4-pentenoic acid) and 4.4'-dien-VPA (2-(2-propenyl-4-pentenoic acid) detected only in low concentration. The amino acid pattern in plasma was characterized by a decrease or branched chain amino acids by 50% in contrast to the increase of the aromatic amino acids. Methionine, however, was in the normal range. Due to lack of a biochemical parameter indicating a possibly irreversible development of VPA induced hepatotoxicity stopping of VPA therapy should be obligatory if abnormal unsaturated VPA metabolites are detected or if dien-VPA/3, a normal metabolic compound, is increased above the normal range. L-carnitine treatment is recommended as a prophylactic therapy.


Radioprotective potential of Rosemarinus officinalis against lethal effects of gamma radiation : a preliminary study.
The radioprotective effect of Rosemarinus officinalis extract (ROE) was studied in mice exposed to 8 Gy of gamma radiation. The optimum dose for radioprotection was determined by administering 100, 200, 400, 800, 1000, 1500, and 2000 mg/kg body weight of ROE orally once daily, consecutively for five days before irradiation. Treatment of mice with ROE, delayed the onset of mortality and reduced the symptoms of radiation sickness when compared with the non-drug-treated irradiated controls. The dose of ROE found to be most effective against radiation was 1000 mg/kg body weight because this dose increased the survival time and reduced the mortality rate of mice significantly. Body weight loss in ROE administered irradiated animals was significantly less in comparison with animals who were given radiation treatment alone. Furthermore, irradiation of animals resulted in an elevation in lipid peroxidation (LPx) and a significant decrease in glutathione (GSH) in blood and liver. Conversely, administration of animals with ROE before irradiation caused a significant decline in LPx accompanied by a significant increase in GSH concentration. The present study demonstrates that Rosemarinus officinalis leave extract is a good radioprotector.


Characterization of a vacuolar pyrophosphatase in Trypanosoma brucei and its localization to acidocalcisomes.
Inorganic pyrophosphate promoted the acidification of an intracellular compartment in permeabilized procyclic trypomastigotes of Trypanosoma brucei, as measured by acridine orange uptake. The proton gradient generated by pyrophosphate was collapsed by addition of nigericin or NH(4)Cl. Pyrophosphate-driven proton translocation was stimulated by potassium ions and inhibited by KF, by the pyrophosphate analogs imidodiphosphate and aminomethylenediphosphonate (AMDP), and by the thiol reagent p-hydroxymercuribenzoate at concentrations similar to those that inhibit the plant vacuolar H(+)-pyrophosphatase (PPase). The proton translocation activity had a pH optimum around 7.5 and was partially inhibited by 7-chloro-4-nitrobenz-2-oxa-1,3-diazole (10 microM) and unaffected by bafilomycin A(1) (40 nM), concanamycin A (5 nM), sodium o-vanadate (500 microM), oligomycin (1 microM), N-ethylmaleimide (100 microM), and KNO(3). AMDP-sensitive pyrophosphate hydrolysis was detected in both procyclic and bloodstream trypomastigotes. Measurements of acridine orange uptake in permeabilized procyclic trypomastigotes in the presence of different substrates and inhibitors suggested the presence of H(+)-ATPase, H(+)-PPase, and (ADP-dependent) H(+)/Na(+) antiport activity in the same compartment. Separation of bloodstream and procyclic trypomastigote extracts on Percoll gradients yielded fractions that contained H(+)-PPase (both stages) and H(+)/Na(+) exchanger (procyclics) activities but lacked markers for mitochondria, glycosomes, and lysosomes. The organelles in these fractions were identified by electron microscopy and X-ray microanalysis as acidocalcisomes (electron-dense vacuoles). These results provide further evidence for the unique nature of acidocalcisomes in comparison with other, previously described, organelles.


Psychopathic personality traits in middle-aged male twins: a behavior genetic investigation.
Psychopathic personality is characterized by interpersonal dominance, impulsivity, sensation seeking, poor planning, and aggressiveness. Studies have shown that the Multidimensional Personality Questionnaire (MPQ) can be used to estimate scores on the fearless-dominant (FD) and the impulsive-antisocial (IA) dimensions of the Psychopathic Personality Inventory (PPI), the best validated self-report measure of psychopathic personality traits. Prior behavior genetic studies reported roughly equal genetic and nonshared environmental influences for both FD and IA, which remained stable from adolescence to young adulthood. However, no prior studies address genetic and environmental influences on these dimensions beyond early adulthood. We utilized the classic twin method to examine genetic and environmental influences on variance in FD and IA in a sample of middle-aged male twins. Biometric modeling indicated that the variance in both factors is best explained by additive genetic and nonshared environmental influences. FD showed roughly equal contributions from genetic and environmental factors, whereas IA showed greater contributions from environmental than genetic factors. Additionally, the small phenotypic correlation between FD and IA was explained entirely by nonshared environmental factors.


Overdose of lomustine: report of two cases.
Two male patients with high-grade gliomas were treated with subtotal or total resection and radiotherapy followed by a lomustine-containing chemotherapy regimen. Both patients took lomustine at an oral dose of 800 mg over five days instead of their regular doses of 200 and 240 mg. Grade 4 neutropenia and thrombocytopenia developed in both patients within two weeks of the last lomustine dose. One of them was admitted to hospital because of febrile neutropenia. Neutropenia and thrombocytopenia were detected in the other patient when he was examined in the emergency room following a generalized convulsion. Both patients recovered from the severe myelosuppression caused by lomustine. No other organ toxicities were observed.


Burnout in occupational therapists and physical therapists working in head injury rehabilitation.
Burnout has been linked to job retention in occupational therapy, physical therapy, and other health professions. Professional development activities are often suggested to reduce burnout, but little empirical evidence supports this contention. This study explored the prevalence of burnout among occupational and physical therapists working in head injury rehabilitation and evaluated the relationship between burnout and professional development activities. Forty therapists working full-time in head injury rehabilitation were surveyed. Correlations between subscale scores of the Maslach Burnout Inventory (i.e., Emotional Exhaustion, Depersonalization, and Personal Accomplishment) and responses to a survey of professional development activities are reported. Professional development activities are most strongly associated with feelings of personal accomplishment. Emotional exhaustion was relatively high among these therapists, but few feelings of depersonalization were evident. Professional development activities in the workplace may augment feelings of personal accomplishment and minimize burnout as an issue in job retention. Strategies to effectively identify and manage therapists' feelings of emotional exhaustion require further study.


Deep Learning Modeling of Androgen Receptor Responses to Prostate Cancer Therapies.
Gain-of-function mutations in human androgen receptor (AR) are among the major causes of drug resistance in prostate cancer (PCa). Identifying mutations that cause resistant phenotype is of critical importance for guiding treatment protocols, as well as for designing drugs that do not elicit adverse responses. However, experimental characterization of these mutations is time consuming and costly; thus, predictive models are needed to anticipate resistant mutations and to guide the drug discovery process. In this work, we leverage experimental data collected on 68 AR mutants, either observed in the clinic or described in the literature, to train a deep neural network (DNN) that predicts the response of these mutants to currently used and experimental anti-androgens and testosterone. We demonstrate that the use of this DNN, with general 2D descriptors, provides a more accurate prediction of the biological outcome (inhibition, activation, no-response, mixed-response) in AR mutant-drug pairs compared to other machine learning approaches. Finally, the developed approach was used to make predictions of AR mutant response to the latest AR inhibitor darolutamide, which were then validated by in-vitro experiments.


The EVT tube and bifurcated endograft systems: technical considerations and clinical summary. EVI Investigators.
Endovascular exclusion of abdominal aortic aneurysms (AAAs) is an investigational technique under scrutiny around the world. The tube and bifurcated versions of the Endovascular Grafting System (EGS) developed by Endovascular Technologies are the subjects of FDA-approved multicenter trials in the United States (US). Similar studies are under way in Europe, Australia, and the United Kingdom. This review details the implantation techniques for the EGS device and summarizes the important clinical findings published through 1996. Although the EGS was voluntarily removed from the US trial when fractures were discovered in the graft attachment system, subsequent experience with the re-engineered EGS has been positive. Successfully implanted EGS tube grafts have been associated with aneurysm shrinkage after 1 year in AAAs initially excluded or with sealed endoleaks. Aneurysm enlargement has been seen in EGS tube grafts with persistent endoleak.


Quantitative organellar proteomics analysis of rough endoplasmic reticulum from normal and acute pancreatitis rat pancreas.
The rough endoplasmic reticulum (RER) is a central organelle for synthesizing and processing digestive enzymes and alteration of ER functions may participate in the pathogenesis of acute pancreatitis (AP). To comprehensively characterize the normal and diseased RER subproteome, this study quantitatively compared the protein compositions of pancreatic RER between normal and AP animals using isobaric tags (iTRAQ) and 2D LC-MALDI-MS/MS. A total of 469 unique proteins were revealed from four independent experiments using two different AP models. These proteins belong to a large number of functional categories including ribosomal proteins, translocon subunits, chaperones, secretory proteins, and glyco- and lipid-processing enzymes. A total of 37 RER proteins (25 unique in arginine-induced, 6 unique in caerulein-induced and 6 common in both models of AP) showed significant changes during AP including translational regulators and digestive enzymes, whereas only mild changes were found in some ER chaperones. The six proteins common to both AP models included a decrease in pancreatic triacylglycerol lipase precursor, Erp27, and prolyl 4-hydroxylase beta polypeptide as well as a dramatic increase in fibrinogen alpha, beta and gamma chains. These results suggest that the early stages of AP involve changes of multiple RER proteins that may affect the synthesis and processing of digestive enzymes.


Atlantic wolf-fish Anarhichas lupus population diversity: growth and maturation.
Biological data from 1125 female Atlantic wolf-fish Anarhichas lupus were collected during 2002-2006 at their main spawning and fishing grounds in Iceland. The results demonstrated substantial annual variation in growth and maturity of female A. lupus. The fast growing females mature earlier than the slow growing ones. In addition, females mature at a larger size and greater age in warmer temperatures than colder ones. There was a strong negative relationship between temperature and growth, which may indicate that the sea temperature west of Iceland has risen above the optimum for growth of female A. lupus and thereby reduced the reproductive potential of the species.


A double determinant radioimmunoassay Mov2-MOv8 for monitoring ovarian carcinomas: definition of the methodology.
A double-determinant radioimmunoassay for the detection of circulating antigens associated with human ovarian carcinoma was developed using two monoclonal antibodies: MOv2 and MOv8 employed respectively as catcher and tracer. The development of the method through three different procedures enabled us to detect the presence of CaMOv2-CaMOv8 carrying molecules in 14 out of 15 ascitic fluids from ovarian carcinoma patients whose tumors were found to be positive with MOv2 and MOv8 monoclonal antibodies by immunofluorescence. Moreover, 13 out of 15 ovarian carcinoma patients presented high levels of antigen in their serum (60-170 Ua/ml). Low levels of antigen were observed in the normal population, the values ranging from 30-40 Ua/ml. However, in 13 out of 100 apparently healthy women high levels of antigen were found in the serum.


Influence of nicotine in cigarette smoke on acute ventilatory responses in awake dogs.
To determine whether the acute ventilatory responses to inhaled cigarette smoke are affected by a difference in nicotine level, control cigarettes (low-nicotine research cigarettes) were laced with nicotine to generate an increase of 330% (mean) in nicotine content with little or no change in the levels of other smoke constituents. Acute ventilatory responses to both control and nicotine-laced cigarettes were determined and compared in six awake chronic dogs. Spontaneous inhalation of nicotine-laced cigarette smoke (10% concn, 750 ml vol) via a tracheostomy tube caused distinct and consistent changes in breathing pattern on the first or second breath of inhaled smoke: an apnea in three dogs, an augmented inspiration in two dogs, and rapid shallow breathing in one dog. No significant change in breathing pattern was found immediately following inhalation of control cigarette smoke. Both types of cigarettes caused a delayed hyperpnea. However, the increase in minute ventilation induced by nicotine-laced cigarettes (from a base line of 2.8 to a peak of 25.7 l/min) was significantly greater than that by control cigarettes (from 2.9 to 5.5 l/min). Results of this study suggest that nicotine is responsible for the elicitation of both the immediate and delayed ventilatory responses to inhaled cigarette smoke generated under our experimental conditions.


Catastrophic massive intracardiac thrombus in a 40-year-old patient with dilated cardiomyopathy.
Dilated cardiomyopathy has been associated with left ventricular (LV) thrombosis which leads to substantial morbidity and mortality as a site for systemic emboli. We report an interesting case of a stroke and acute limb ischemia secondary to a large mobile pedunculated LV thrombus in 40-year-old patient with dilated cardiomyopathy.