Photodissociation of singlet oxygen in the UV region.
Photodissociation of singlet oxygen, O2 a(1)Δg, by ultraviolet radiation in the region from 200 to 240 nm has been investigated using velocity map imaging of the atomic oxygen photofragments. Singlet oxygen molecules are generated in a pulsed discharge and studied by one-laser photodissociation and detection around 226 nm as well as two color photodissociation at various wavelengths in the range from 200 to 240 nm. A simple model of the discharge on and off signal indicates efficient conversion of O2 X(3)Σg(-)(v = 0) in the parent beam to O2 a(1)Δg(v = 0-2). Minute amounts of highly excited vibrational levels of ground state O2 X(3)Σg(-)(v > 0) are detected but no evidence is found for production of the O2 b(1)Σg(+) state. Over the decreasing wavelength range 240-200 nm the a(1)Δg-state signal relative to the X(3)Σg(-)(v = 0) signal decreases strongly. Around 226 nm the a(1)Δg(v = 0-2) states averaged branching ratio percentage for O((3)Pjj = 2 : 1 : 0) is found to be 56 : 36 : 8 (±5%), respectively. The anisotropy parameter for photodissociation of a(1)Δg(v = 0-2) averages to β = 1.3 ± 0.4. The a(1)Δg(v = 0) photodissociation cross section is found to 3-10 times stronger than theory predicts. Furthermore, the photodissociation image shows a strong parallel character, (i.e., transition moment parallel to the molecular axis) while theory predicts a predominantly negative character.


Pacing as a strategy to improve energy management in myalgic encephalomyelitis/chronic fatigue syndrome: a consensus document.
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating condition characterized by a number of symptoms which typically worsen following minimal exertion. Various strategies to manage the limited energy levels have been proposed. Of these, pacing has been consistently rated as one of the most helpful in surveys conducted by patient groups. This review is a response to the paucity of the information on pacing in the scientific literature. We describe the principle of pacing and how this can be adapted to meet individual abilities and preferences. A critical evaluation of the research was conducted to ascertain the benefits and limitations of this strategy. Based on various studies, it is proposed that pacing can help to stabilize the condition and avoid post-exertional malaise. Pacing offers practitioners an additional therapeutic option which is acceptable to the majority of patients and can reduce the severity of the exertion-related symptoms of ME/CFS.


Kidney injuries in professional American football: implications for management of an athlete with 1 functioning kidney.
The frequency and severity of kidney injuries and their impact on return to play in American football has not been described in the literature. Our objective is to identify the number of kidney injuries in the National Football League (NFL) and the effect of these injuries. Case series; Level of evidence, 4. All kidney injuries in the NFL from 1986 to 2004 were reviewed, including the type and mechanism of injury, treatment, and time to return to play. In addition, NFL physicians and athletic trainers were asked if they were aware of any football player at the professional, collegiate, or high school levels who had lost a kidney and how they would advise a football player with only 1 functioning kidney. A total of 52 cases of renal injuries were identified, an average of 2.7 cases per season. The rate of kidney injury was 10 times greater during games (0.000055 per exposure) than practices (0.000005 per exposure) (P < .0001). The most common injury was kidney contusion (42), followed by kidney laceration (6) and kidney stones and dysfunction (2 each). Almost all the injuries were contact related (49). More than a third of the players required hospitalization for their injury (18), although none required surgery. All the athletes returned to play. The most days missed were after a kidney laceration (mean, 59.8), followed by kidney contusion (15.1) and dysfunction (14.0). While 61% of respondents would allow a professional athlete with only 1 kidney to play, approximately 50% would advise a college athlete with only 1 functioning kidney not to play football, and 60% would advise a similar high school athlete not to play. Renal trauma is a rare but potentially debilitating injury in the NFL, with players at greater risk during games. Most players recover to play, but it may take some time, especially with a kidney laceration. It may be safe for players with only 1 functioning kidney to play in the NFL.


The treatment and prevention of knee osteoarthritis: a tool for clinical decision-making.
Osteoarthritis (OA) is a major cause of disability, which will increase further with longer lifetime and higher average weight of the population. To review a hierarchy of interventions for OA in clinical practice, and compare it with the Strength of Recommendation (SOR) proposed by the Osteoarthritis Research Society International (OARSI). Search for relevant randomized controlled trials in databases, as well as published systematic reviews and meta-analyses. Preventive measures are few and uncertain; however, basic therapy includes reduction in weight in the obese and exercises to keep in shape; this is in accordance with the OARSI guidelines (OARSI, 100% consensus) emphasizing the need for obese individuals with knee OA to lose weight (OARSI, SOR = 96%). There are indications of an effect of some nutraceuticals, though further studies are needed for validation (OARSI, SOR = 63%). Pharmacological treatment has paracetamol as primary prescription, which is a safe, albeit weak analgesic. Supplementary medications are prescribed according to level of pain and possible inflammation.


Traumatic brain injury in the prodromal period of Parkinson's disease: A large epidemiological study using medicare data.
Studies suggest a greater risk of Parkinson's disease (PD) after traumatic brain injury (TBI), but it is possible that the risk of TBI is greater in the prodromal period of PD. We aimed to examine the time-to-TBI in PD patients in their prodromal period compared to population-based controls. We identified 89,790 incident PD cases and 118,095 comparable controls aged > 65 years in 2009 using Medicare claims data. Using data from the preceding 5 years, we compared time-to-TBI in PD patients in their prodromal period to controls. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for TBI in a Cox regression, while adjusting for age, sex, race/ethnicity, modified Charlson comorbidity index, smoking, and alcohol use. Risk of TBI was greater in PD patients in their prodromal period across all age and sex groups, with HRs consistently increasing with proximity to PD diagnosis. HRs ranged from 1.64 (95% CI, 1.52, 1.77) 5 years preceding diagnosis to 3.93 (95% CI, 3.74, 4.13) in the year before. The interaction between PD, TBI, and time was primarily observed for TBI attributed to falls. Motor dysfunction and cognitive impairment, suggested by corresponding International Classification of Diseases, Ninth Revision codes, partially mediated the PD-TBI association. There is a strong association between PD and a recent TBI in the prodromal period of PD. This association strengthens as PD diagnosis approaches and may be a result of undetected nonmotor and motor symptoms, but confirmation will be required. Ann Neurol 2017;82:744-754.


Analysis of H2 clearance curves used to measure blood flow in rat sciatic nerve.
1. By use of the H2 clearance technique, blood flow was measured in the sciatic nerve of healthy, anaesthetized Sprague-Dawley rats at rest, during inferior vena cava occlusion and during 5-hydroxytryptamine infusion. The purpose was to clarify the mechanisms underlying the biexponential curves which are commonly obtained using this technique. 2. An analysis of the frequency distribution of rate constants of 270 nerve and thirty-three arterial samples indicated that H2 clearance rates cluster below 20 ml min-1 100 g-1 and between 70 and 100 ml min-1 100 g-1. This suggests that at least two compartments are present. 3. The contribution of diffusion was studied by recording H2 clearance immediately following circulatory arrest. Slow clearance rates (median = 2.4 ml min-1 100 g-1) were observed, indicating that diffusion is not likely to contribute significantly to nutritive flow under most situations. 4. The contribution of arteriovenous shunts to H2 clearance was assessed by determining H2 clearance during inferior vena cava occlusion and the infusion of 5-hydroxytryptamine. Both manoeuvres caused abolition of, or a significant reduction in the weight of, the fast component which indicates that this compartment is closely related to arteriovenous shunts in nerve. 5. By use of a multi-compartmental model, it was shown that H2 clearance should follow a multi-exponential course, where the weights of the components reflect the relative volumes of each compartment and the exponents represent the relative flow (i.e. flow per unit volume) in each compartment. 6. By use of other mathematical models, estimates were made for the clearance rates attributable to polarographic oxidation of H2 at the tip of the microelectrode (0.2 ml min-1 100 g-1) and to diffusion to air (2 ml min-1 100 g-1). The latter estimate is very close to the measured value of 2.4 ml min-1 100 g-1. 7. These findings indicate that it is possible to separately assess nutritive and non-nutritive flow by application of biexponential analysis to H2 clearance curves. The data suggest that the fast component of a H2 clearance curve is closely associated with arteriovenous shunts, while the slower component is likely to represent capillary flow. Processes such as diffusion to air or oxidation of H2 by the electrode are very slow and therefore are unlikely to distort the assessment of blood flow by using this technique.


Predicting length of stay and mortality among hospitalized patients with type 2 diabetes mellitus and hypertension.
Type 2 diabetes mellitus (T2DM) and hypertension (HTN), both non-communicable diseases, are leading causes of death globally, with more imbalances in lower middle-income countries. Furthermore, poor treatment and management are known to lead to intensified healthcare utilization and increased medical care costs and impose a significant societal burden, in these countries, including Indonesia. Predicting future clinical outcomes can determine the line of treatment and value of healthcare costs, while ensuring effective patient care. In this paper, we present the prediction of length of stay (LoS) and mortality among hospitalized patients at a tertiary referral hospital in Tasikmalaya, Indonesia, between 2016 and 2019. We also aimed to determine how socio-demographic characteristics, and T2DM- or HTN-related comorbidities affect inpatient LoS and mortality. We analyzed insurance claims data of 4376 patients with T2DM or HTN hospitalized in the referral hospital. We used four prediction models based on machine-learning algorithms for LoS prediction, in relation to disease severity, physician-in-charge, room type, co-morbidities, and types of procedures performed. We used five classifiers based on multilayer perceptron (MLP) to predict inpatient mortality and compared them according to training time, testing time, and Area under Receiver Operative Curve (AUROC). Classifier accuracy measures, which included positive predictive value (PPV), negative predictive value (NPV), F-Measure, and recall, were used as performance evaluation methods. A Random forest best predicted inpatient LoS (R2, 0.70; root mean square error [RMSE], 1.96; mean absolute error [MAE], 0.935), and the gradient boosting regression model also performed similarly (R2, 0.69; RMSE, 1.96; MAE, 0.935). For inpatient mortality, best results were observed using MLP with back propagation (AUROC 0.899; 69.33 and 98.61 for PPV and NPV, respectively). The other classifiers, stochastic gradient descent with regression loss function, Huber, and random forest models all showed an average performance. Linear regression model best predicted LoS and mortality was best predicted using MLP. Patients with primary diseases such as T2DM or HTN may have comorbidities that can prolong inpatient LoS. Physicians play an important role in disseminating health related information. These predictions could assist in the development of health policies and strategies that reduce disease burden in resource-limited settings.


Dynamic Interaction between Cortico-Brainstem Pathways during Training-Induced Recovery in Stroke Model Rats.
Reorganization of residual descending motor circuits underlies poststroke recovery. We previously clarified a causal relationship between the cortico-rubral tract and intensive limb use-induced functional recovery after internal capsule hemorrhage (ICH). However, other descending tracts, such as the cortico-reticular tract, might also be involved in rehabilitation-induced compensation. To investigate whether rehabilitation-induced recovery after ICH involves a shift in the compensatory circuit from the cortico-rubral tract to the cortico-reticular tract, we established loss of function of the cortico-rubral tract or/and cortico-reticular tract using two sets of viral vectors comprising the Tet-on system and designer receptors exclusively activated by the designer drug system. We used an ICH model that destroyed almost 60% of the corticofugal fibers. Anterograde tracing in rehabilitated rats revealed abundant sprouting of axons from the motor cortex in the red nucleus but not in the medullary reticular formation during the early phase of recovery. This primary contribution of the cortico-rubral tract was demonstrated by its selective blockade, whereas selective cortico-reticular tract silencing had little effect. Interestingly, cortico-rubral tract blockade from the start of rehabilitation induced an obvious increase of axon sprouting in the reticular formation with substantial functional recovery. Additional cortico-reticular tract silencing under the cortico-rubral tract blockade significantly worsened the recovered forelimb function. Furthermore, the alternative recruitment of the cortico-reticular tract was gradually induced by intensive limb use under cortico-rubral tract blockade, in which cortico-reticular tract silencing caused an apparent motor deficit. These findings indicate that individual cortico-brainstem pathways have dynamic compensatory potency to support rehabilitative functional recovery after ICH.SIGNIFICANCE STATEMENT This study aimed to clarify the interaction between the cortico-rubral and the cortico-reticular tract during intensive rehabilitation and functional recovery after capsular stroke. Pathway-selective disturbance by two sets of viral vectors revealed that the cortico-rubral tract was involved in rehabilitation-induced recovery of forelimb function from an early phase after internal capsule hemorrhage, but that the cortico-reticular tract was not. The sequential disturbance of both tracts revealed that the cortico-reticular tract was recruited and involved in rehabilitation-induced recovery when the cortico-rubral tract failed to function. Our data demonstrate a dynamic compensatory action of individual cortico-brainstem pathways for recovery through poststroke rehabilitation.


Hemoglobinopathies in North Africa: a review.
Hemolytic anemias are very common diseases. Among these diseases, hemoglobinopathies are widely spread throughout the Mediterranean Basin, including North Africa (Tunisia, Algeria and Morocco). Their severity and disabling nature make them a major public health problem. This study includes our data on the Tunisian hemoglobinopathies together with all the reports concerning epidemiological, clinical and molecular aspects in Algerian and Moroccan populations. Investigation methods begin with the application of several techniques for hemoglobin (Hb) analyses [electrophoresis and isoelectric focusing (IEF), micro-chromatography assay] of anemic patients in various hospital departments. Molecular investigation by DNA analyses completes the hematological and biochemical studies using polymerase chain reaction (PCR) followed by enzymatic digestion and/or denaturing gradient gel electrophoresis (DGGE), single strand conformation polymorphism (SSCP) and sequencing. These methods offer screening for a large number of families affected by sickle cell disease and thalassemia. In Tunisia, Algeria, and Morocco, more than 45 mutations have been identified on the beta-globin gene. The most common in Tunisia and in Algeria are codon 39 (C>T) and IVS-I-110 (G>A), which together account for more than 50% of all mutations. In Morocco, the predominant mutations are codon 39 and frameshift codon (FSC) 8 (-AA). The identification of molecular defects in the betagene contributes to the development of diagnostic tests (prenatal diagnosis), and gives us the opportunity to help many couples. Our studies of the haplotypes of the beta(S), codon 39 and IVS-I-110 origins allowed the hypothesis of a Benin origin for beta(S), a local North African origin for codon 39 and an Eastern Mediterranean origin for IVS-I-110. The analysis of polymorphisms associated with a moderate phenotype of beta-thalassemia (beta-thal) and sickle cell disease in North Africa has shown, in several cases, a strong association with some mutations and restriction fragment length polymorphisms (RFLP) haplotype IX on the beta-globin locus and the -158 (C>T) polymorphism in 5' on the (G)gamma-globin gene. Finally, more knowledge on the regulation of the beta-globin locus may contribute to the improvement of investigation, monitoring and treatment of hemoglobinopathies.


An investigation into the health-related quality of life of individuals living with HIV who are receiving HAART.
The health authorities have recently accepted the routine provision of highly active antiretroviral therapy to persons living with AIDS in South Africa. There is a need to investigate the impact of HAART on the health-related quality of life of people living with HIV/AIDS (PLWHA) in a resource-poor environment, as this will have an influence on compliance and treatment outcome. The aim of this study was to explore whether HAART is efficacious in improving the self-reported health-related quality of life (HRQoL) in a group of PWLA in WHO Stages 3 and 4 living in a resource-poor community. A quasi-experimental, prospective repeated measures design was used to monitor the HRQoL over time in participants recruited to an existing HAART programme. The HRQoL of 117 participants was determined through the use of the Xhosa version of the EQ-5D and measurements were taken at baseline, one, six and 12 months. At the time of the 12-month questionnaire, 95 participants had been on HAART for 12 months. Not all participants attended all follow-up visits, but only two participants had withdrawn from the HAART programme, after two or three months. At baseline, the rank order of problems reported in all domains of the EQ-5D was significantly greater than at 12 months. The mean score on the global rating of health status increased significantly (p < 0.001) from a mean of 61.7 (SD = 22.7) at baseline to 76.1 at 12 months (SD = 18.5) It is concluded that, even in a resource-poor environment, HRQoL can be greatly improved by HAART, and that the possible side effects of the drugs seem to have a negligible impact on the wellbeing of the subjects. This bodes well for the anticipated roll-out of HAART within the public health sector in South Africa.


Systematic review of the incidence and consequences of uterine rupture in women with previous caesarean section.
To evaluate the incidence and consequences of uterine rupture in women who have had a delivery by caesarean section. Systematic review. Medline, HealthSTAR, Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, National Centre for Reviews and Dissemination, reference lists, and national experts. Studies in all languages were eligible if published in full. Methodological quality was evaluated for each study by using criteria from the United States Preventive Services Task Force and the National Health Service Centre for Reviews and Dissemination. Uterine rupture was categorised as asymptomatic or symptomatic. We reviewed 568 full text articles to identify 71 potentially eligible studies, 21 of which were rated at least fair in quality. Compared with elective repeat caesarean delivery, trial of labour increased the risk of uterine rupture by 2.7 (95% confidence interval 0.73 to 4.73) per 1000 cases. No maternal deaths were related to rupture. For women attempting vaginal delivery, the additional risk of perinatal death from rupture of a uterine scar was 1.4 (0 to 9.8) per 10,000 and the additional risk of hysterectomy was 3.4 (0 to 12.6) per 10 000. The rates of asymptomatic uterine rupture in trial of labour and elective repeat caesarean did not differ significantly. Although the literature on uterine rupture is imprecise and inconsistent, existing studies indicate that 370 (213 to 1370) elective caesarean deliveries would need to be performed to prevent one symptomatic uterine rupture.


Secondary prevention measures in anaphylaxis patients: Data from the anaphylaxis registry.
Patients with a history of anaphylaxis are at risk of future anaphylactic reactions. Thus, secondary prevention measures are recommended for these patients to prevent or attenuate the next reaction. Data from the Anaphylaxis Registry were analyzed to identify secondary prevention measures offered to patients who experienced anaphylaxis. Our analysis included 7788 cases from 10 European countries and Brazil. The secondary prevention measures offered varied across the elicitors. A remarkable discrepancy was observed between prevention measures offered in specialized allergy centers (84% of patients were prescribed adrenaline autoinjectors following EAACI guidelines) and outside the centers: Here, EAACI guideline adherence was only 37%. In the multivariate analysis, the elicitor of the reaction, age of the patient, mastocytosis as comorbidity, severity of the reaction, and reimbursement/availability of the autoinjector influence physician's decision to prescribe one. Based on the low implementation of guidelines concerning secondary prevention measures outside of specialized allergy centers, our findings highlight the importance of these specialized centers and the requirement of better education for primary healthcare and emergency physicians.


Motor abilities of adolescents with a disruptive behavior disorder: The role of comorbidity with ADHD.
The aim of this study was to explore the incidence, type and severity of motor impairment in male adolescents with a disruptive behavior disorder (DBD) and evaluate the role of comorbid ADHD. The Bruininks-Oseretsky test of motor proficiency, Second Edition was administered to examine a detailed motor profile and to compare the motor abilities of individuals with DBD (n = 99) to those of controls (n = 87). Additional subgroup analyses were conducted within the clinical population and encompassed (1) analyzing differences in motor profiles between individuals diagnosed with oppositional defiant disorder (ODD) or conduct disorder (CD) and (2) comparing the motor profiles of individuals with or without comorbid ADHD. The results indicated that individuals with a DBD showed a mixed motor impairment profile. Even after controlling for IQ, the DBD group obtained significantly lower scores in comparison to controls. The ODD and CD subgroups showed a similar motor profile. Presence of comorbid ADHD did not produce major differences in the motor profile. As approximately 79% of the adolescents with a DBD suffered from motor impairment, motor ability needs to be adequately addressed in research as well as in clinical practice.


Residency effects in animal contests.
The question of why territorial residents usually win asymmetrical owner-intruder contests is critical to our understanding of animal contest evolution. Game theory suggests that, under certain conditions, residency could be used as an arbitrary means of contest settlement in a manner analogous to tossing a coin. Key empirical support for this idea is provided by a study on the speckled wood butterfly (Pararge aegeria); however, this result has proven controversial. We show conclusively that residency does not serve as an arbitrary cue for contest settlement in this species. By means of a series of manipulative experiments, conducted on two phenotypically divergent populations of P. aegeria, we also rule out the recently presented alternative that contests are settled due to resource-correlated asymmetries in thoracic temperature. Our results instead suggest that more intrinsically aggressive males accumulate as residents and continue to win due to the self-reinforcing effect of prior winning experience. Truly arbitrary contest settlement may be rare or non-existent in the wild.


Survival and functional outcome of children requiring endotracheal intubation during therapy for severe traumatic brain injury.
To determine the predictors of survival and functional outcome of pediatric patients with traumatic brain injury severe enough to require endotracheal intubation and mechanical ventilation. Retrospective, observational cohort study. Pediatric intensive care unit (ICU) at a tertiary care children's hospital. All children (n = 105) admitted over a 5-yr period with traumatic brain injury severe enough to require endotracheal intubation and mechanical ventilation. The median age was 43 months (range 1 month to 14 yrs). Of these children, 74% were male and 70% were white. None. Variables studied included vital signs during the first 24 hrs of admission, Pediatric Risk of Mortality (PRISM) score, Glasgow Coma Score, duration of mechanical ventilation, and number of pediatric ICU and hospital days. Functional status was graded as normal, independent, partially dependent, or dependent in the areas of locomotion, self-care, and communication. This status was assessed at hospital discharge by chart review and at follow-up by telephone interview. The median Glasgow Coma Score was 6 (range 3 to 14) and the median PRISM score was 13 (range 1 to 51). There were 19 (18.1%) deaths, 17 in the pediatric ICU and two after hospital discharge. Of the patients who survived to hospital discharge, 39 (37.1%) patients were completely normal or independent, 42 (40%) patients were partially dependent, and seven (6.7%) patients were dependent in all three areas of function. Follow-up evaluations were available for 80 patients, with a median follow-up time of 24.5 months (range 8 to 70). Of the 78 patients who survived and were available for follow-up, the number who were functionally normal or independent increased to 69 (65.7%). At follow-up, there were eight (7.6%) patients remaining with partial dependency in at least one area of function while one (0.9%) patient continued to be dependent in all three areas of function. Mortality and dependent functional outcome were more likely in patients with younger age, lower Glasgow Coma Score, and higher PRISM score at hospital admission. Of the 27 patients with a Glasgow Coma Score of < or = 5, 11 (40.7%) survived with normal or independent functional status at follow-up. Of the 24 patients with PRISM scores of > 20, only five (20.8%) were functionally normal or independent at follow-up. The relative risk of a bad outcome for patients with a Glasgow Coma Score of < or = 5 and a PRISM score of > or = 20 was ten times higher than the group of patients with a Glasgow Coma Score of < or = 5 but a PRISM score of < 20. Children with severe traumatic brain injury who survive to hospital discharge will continue to improve in their functional status over the next few years. Although low Glasgow Coma Score is strongly associated with death or poor functional outcome after therapy for traumatic brain injury, many patients with Glasgow Coma Score of < or = 5 can survive with good function. PRISM scores add to the power of Glasgow Coma Score to predict survival and functional outcome in tracheally intubated pediatric patients with Glasgow Coma Score of < or = 5.


In vivo effects of pegylated recombinant human megakaryocyte growth and development factor on hematopoiesis in normal mice.
The in vivo effects of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF), a truncated molecule of recombinant human thrombopoietin modified with polyethylene glycol, were investigated in normal Balb/c mice. PEG-rHuMGDF was more potent in producing platelets and the dose-response curve was steeper compared with the case of the nonpegylated form of this molecule. Five consecutive injections with PEG-rHuMGDF caused a dose-dependent increase in peripheral platelet counts with a peak on day 8. There was a dose-dependent rise in platelet counts on day 8 at daily doses from 0.333 to 30 micrograms/kg. Intermediate doses of PEG-rHuMGDF (1.111 to 10 micrograms/kg/day) caused a significant decrease in mean platelet volume, and conversely, higher doses of PEG-rHuMGDF (30 to 270 micrograms/kg/day) induced a dose-dependent increase in mean platelet volume. There was a dose-dependent decrease in hemoglobin concentration with a minimum on day 8 but no significant reduction in reticulocyte counts following PEG-rHuMGDF administration. White blood cell counts were unchanged by PEG-rHuMGDF treatment. Marrow megakaryocyte size enlarged to 1.5-fold and the number of marrow megakaryocytes increased to sixfold by consecutive administration of PEG-rHuMGDF at 30 micrograms/kg/day. A twofold increase in the number of marrow megakaryocytic progenitor cells (colony-forming units-megakaryocyte) was also observed. Marrow erythroid progenitor (colony-forming units-erythroid) counts decreased but splenic colony-forming units-erythroid, marrow and splenic erythro/myeloid progenitor cell counts, and splenic granulocyte/macrophage progenitor cell counts increased with PEG-rHuMGDF treatment. Marrow and splenic erythroid burst-forming cells were unchanged. These results indicate that PEG-rHuMGDF, a truncated molecule of thrombopoietin, is a potent stimulator for megakaryopoiesis and thrombopoiesis, and also affects the development of other hematopoietic cells in normal mice.


[Parental stress in children undergoing congenital heart surgery].
The caregivers of children with congenital heart disease undergoing cardiac surgery are under stress due to the uncertainty of the surgical outcome and the stressful experience of being admitted in an intensive care unit. The current review describes the factors associated with parental stress in patients with congenital heart disease undergoing cardiac surgery. These factors can be grouped into factors related to the patient, the parents, the environment and the clinical team. The loss of the parental role, the physical appearance and the child's behavior during their stay in the intensive care unit are identified as the most powerful sources of stress. An information program to be given to the caregivers before cardiac surgery should include all these factors as a central part of its contents, should significantly reduce the levels of parental stress and must be included in the process of admitting a patient for congenital heart surgery.


Adverse events related to low dose corticosteroids in autoimmune hepatitis.
Autoimmune hepatitis requires long-term therapy, and systemic corticosteroids are the backbone of therapeutic management. Prolonged use of corticosteroids may lead to adverse events but data from long-term studies are mainly derived from studies in rheumatic diseases. To assess cataract, diabetes and fractures in relation to corticosteroid doses in the long-term maintenance treatment of patients with autoimmune hepatitis. We retrospectively collected data on 476 patients (77% women) with an established diagnosis of autoimmune hepatitis. Binary logistic regression with a generalised estimating equation was used to analyse the association between current corticosteroid use and the incidence of cataract, diabetes and fractures with onset after autoimmune hepatitis diagnosis. We corrected for sex, age, cirrhosis at diagnosis and predniso(lo)ne use in the prior 3 years to account for possible ongoing effects. A total of 6634 years, with a median of 13 (range 1-40) per patient were recorded. The median age at diagnosis was 44 years (range 2-88). Adverse events were documented in 120 (25%) patients. Low-dose predniso(lo)ne (0.1-5.0 mg/d) increased the odds of fractures whereas higher doses (>5.0 mg/d) increased the odds of cataracts and diabetes. Budesonide increased the odds of cataract and fractures; this effect was independent of predniso(lo)ne use in the prior 1, 2 or 3 years. Even low doses of corticosteroids frequently lead to substantial adverse events refuting the assumption that adverse events are prevented by administering low doses.


Cognitive impairment among the elderly in a rural community in Malaysia.
Cognitive impairment is common in late life and may be due to the normal process of ageing or associated with physical or mental disorders. The aim of this study was to determine the prevalence of cognitive impairment among the elderly in a rural community setting. A cross sectional study design using stratified proportionate cluster sampling method was used in this study. A questionnaire similar to the Elderly Cognitive Assessment Questionnaire (ECAQ) was used as a screening instrument for cognitive impairment. The prevalence of cognitive impairment was 22.4% (50/223) among the elderly respondents. Cognitive impairment among the elderly was significantly associated with age, gender, ethnicity, marital status and level of education.


A quantitative study of rat uterine sympathetic innervation during pregnancy and post partum.
In mammals, pregnancy induces a transient and extensive degeneration of uterine sympathetic innervation. We used the models of unilateral oviduct ligation and in oculo myometrium transplant in pregnant rats to address the role of stretching forces and/or hormone milieu in the loss of sympathetic innervation. The sympathetic fibres of the uterine horn and in oculo myometrial transplants were quantified on tissue sections processed by the glyoxylic acid technique. In normal pregnant rats, the density of uterine horn innervation was significantly reduced at late pregnancy and recovery took place during post partum. The empty horn of pregnant rats showed no significant changes in density of myometrial innervation during pregnancy or post partum. In oculo myometrial transplants were organotypically reinnervated in virgin animals. When the transplants were exposed to gestational hormonal milieu, few or no fibres were observed to the end of pregnancy; however, a significant increase at post partum was observed. Results showed that both the effects of stretching and the hormone milieu derived from the fetus-placenta complex play a role as inductors of changes on sympathetic myometrial innervation during pregnancy and support the idea that immature muscular uterine fibres are more susceptible to the effects of pregnancy than those originating from adult animals.


Sumatriptan: a review of its pharmacokinetics, pharmacodynamics and efficacy in the acute treatment of migraine.
Sumatriptan was developed more than 20 years ago as a 5-HT1B/1D receptor agonist, the first drug in a new class of specific anti-migraine drugs, the triptans. A large amount of information and experience has been gained from the clinical trials undertaken as well the various formulations of sumatriptan used over this period of time. This evaluation specifically reviews the pharmacokinetics, pharmacodynamics, clinical efficacy, and safety of different formulations and dosages of sumatriptan used for the acute treatment of migraines. Special clinical trials of the timing of dosage and sumatriptan in combination with other triptans as well as non-triptan drugs are also included. Oral sumatriptan is effective, but not in a convincing majority (60%) of patients in clinical trials. Sumatriptan has failed to show superiority over more standard and cheaper treatment such as aspirin or aspirin plus metoclopramide. In addition, migraine patients want to quickly become pain free, and to remain pain free, but oral sumatriptan at 100 mg managed to keep patients pain free for 24 h is only 20% of cases. Even though sumatriptan has been a major step forward in providing a new specific therapy for the treatment of migraines, there are still are limitations in its use. There is still an unmet need to develop new non-triptan, anti-migraine drugs which act as effective treatment for those who suffer with migraines.


Characterization of photodamage in coherent anti-Stokes Raman scattering microscopy.
We report a mechanistic analysis of photodamage in coherent anti-Stokes Raman scattering (CARS) microscopy. Photodamage to the myelin sheath in spinal tissues is induced by using the point scan mode and is featured by myelin splitting and shockwaves with broadband emission. Our measurement of photodamage rate versus the excitation power reveals that both linear and nonlinear mechanisms are involved. Moreover, we show that vibrational absorption induced by coherent Raman processes significantly contributes to the nonlinear damage at high peak powers. For CARS imaging of cultured cells, the photodamage is characterized by plasma membrane blebbing and is dominated by a second order mechanism. Our study suggests that for dense samples such as the myelin sheath, CARS imaging induced photodamage can be minimized by using laser beams with relatively long near IR wavelengths and a repetition rate of a few MHz. For less dense samples such as cultured cells, laser pulses of higher repetition rates are preferred.


Zirconium for esthetic rehabilitation: an overview.
The demand for esthetic restorations has resulted in an increased use of dental ceramics for anterior and posterior restorations. A few decades ago, all-ceramic restorations were restricted to treatment in the anterior region, but now all-ceramic restorations can be made anywhere in the dentition. The properties of traditional ceramic materials, however, have limited their use to single crowns; larger restorations have been inadvisable because of insufficient strength. In attempts to meet the requirements for dental materials and improve strength and toughness, several new ceramic materials and techniques have been developed during the past few decades The paper reviews the current literature on dental zirconia with respect to survival, properties, marginal fit, cementation, esthetics and suggests clinical recommendations for their use.


Clinical features and outcomes of COVID-19 in patients with solid tumors: Turkish National Registry Data.
We present demographic, clinical, laboratory characteristics and outcomes of the patients with solid malignancies and novel coronavirus disease (COVID-19) collected from the National COVID-19 Registry of Turkey. A total of 1523 patients with a current or past diagnosis of solid tumors and diagnosed with COVID-19 (confirmed with PCR) between 11 March and 20 May 2020 were included. The primary outcome was 30-day mortality. Median age was 61 (range: 18-94), and 752 (49%) were male. The most common types of cancers were breast (19.8%), prostate (10.9%) and colorectal cancer (10.8%). 65% of the patients had at least one comorbidity. At least one COVID-19-directed therapy was given in 73% of the patients.. Hospitalization rate of the patients was 56.6% and intensive care unit admission rate was 11.4%. Seventy-seven (5.1%) patients died within 30 days of diagnosis. The first multivariate model which included only the demographic and clinical characteristics showed older age, male gender and presence of diabetes and receipt of cytotoxic therapy to be associated with increased 30-day mortality, while breast and prostate cancer diagnoses were associated with lower 30-day mortality. In the second set, we further included laboratory parameters. The presence of leukocytosis (OR 6.7, 95% CI 3.3-13.7, P < .001), lymphocytopenia (OR 3,1, 95% CI 1,6-6,1, P = .001) and thrombocytopenia (OR 3,4 95% CI 1,5-8,1, P = .005) were found to be associated with increased 30-day mortality. Relatively lower mortality compared to Western countries and China mainly results from differences in baseline risk factors but may also implicate the importance of intensive supportive care.


Physical therapists in integrated palliative care: a qualitative study.
The purpose of this study was to explore the perceptions and experiences of physical therapists (PTs) regarding their role in palliative care (PC) when practising in nations with advanced integration of PC into mainstream healthcare. This qualitative study included an electronic demographic survey and semistructured interview. Data analysis included descriptive statistics for demographics and the constant comparative method for interview results. Thirteen PTs from eight nations identified four categories of roles and responsibilities: (1) working with patients and families, (2) being an interdisciplinary team (IDT) member, (3) professional responsibilities beyond direct patient care and (4) factors influencing the role of PTs in PC. Concepts identified were shifting priorities (increased family involvement, emphasis on psychosocial aspects and differences in care philosophy), care across the continuum (accommodating changes in patient status, increasing awareness of PTs' role in varying disease states and working with the IDT) and changing perceptions about PT in PC (perceptions of PTs/others regarding PTs' role in PC and professional responsibilities of the PT in PC). Based on participant responses, a previously published conceptual framework by Wilson et al in 2017 was updated and included an increased emphasis on patient wishes and dignity, treating breathlessness, patient advocacy within their family and use of technology and networking. Within PC, PTs play a key role on the IDT and can improve quality of life; however, multiple barriers exist to providing PT care within PC. Further advocacy is needed from PTs and professional organisations to integrate these services.


Adenosine depletion alters postictal hypoxic cerebral vasodilation in the newborn pig.
Altered postictal cerebral blood flow dilatory responses may contribute to brain injury following neonatal seizures. We developed an initial series of experiments to characterize the effects of seizure activity on cerebral vascular dilatory responses during the immediate postictal period. Significant attenuation of postictal hypoxic cerebral vasodilation was noted. We hypothesize that this diminished cerebral dilator response to hypoxia involves depletion of adenosine (Ado) activity resulting from seizure ictus. Additional experiments were designed to evaluate whether the altered postictal responses were related to a depletion of Ado stores or a decreased response to Ado in the postictal state. Farm-bred piglets were equipped with closed cranial windows. Responses to hypercapnia (10% CO2), hypoxia (fractional inspired O2 = 0.10), and topical sodium nitroprusside (10(-6) M) were compared before and after bicuculline-induced seizures (1 mg/kg). Hypoxia-induced cerebral vasodilation was significantly attenuated in the first 90 min postictal (control: 56.5 +/- 6%, 10 min postictal: 6.3 +/- 2%, 60 min postictal: 21.7 +/- 6%, and 90 min postictal: 21.6 +/- 5%; P < 0.01), whereas the dilator responses to hypercapnia and topical sodium nitroprusside remained intact. In a separate group of piglets, both a dilating (10(-5) M) and a nondilating concentration of Ado (10(-11) M) were topically administered postictally to measure their effects on pial vessel dilatory response to hypoxia. Dilation to topical Ado (10(-5) M) was not altered postictally compared with control. Ado (10(-11) M) restored hypoxia-induced vasodilation to preseizure control values in the immediate postictal period (control: 51.0 +/- 8%, postictal: 46.7 +/- 8%, P > 0.05). Postictal administration of Ado will restore hypoxia-induced cerebral vasodilation in piglets even when a nondilating concentration is employed. This suggests that depletion of Ado with seizure activity is a mechanism for the loss of postictal cerebral vasodilation to hypoxia, and the role of Ado in hypoxic cerebral vasodilation is permissive.


Kombucha fermentation and its antimicrobial activity.
Kombucha was prepared in a tea broth (0.5% w/v) supplemented with sucrose (10% w/v) by using a commercially available starter culture. The pH decreased steadily from 5 to 2.5 during the fermentation while the weight of the "tea fungus" and the OD of the tea broth increased through 4 days of the fermentation and remained fairly constant thereafter. The counts of acetic acid-producing bacteria and yeasts in the broth increased up to 4 days of fermentation and decreased afterward. The antimicrobial activity of Kombucha was investigated against a number of pathogenic microorganisms. Staphylococcus aureus, Shigella sonnei, Escherichia coli, Aeromonas hydrophila, Yersinia enterolitica, Pseudomonas aeruginosa, Enterobacter cloacae, Staphylococcus epidermis, Campylobacter jejuni, Salmonella enteritidis, Salmonella typhimurium, Bacillus cereus, Helicobacterpylori, and Listeria monocytogenes were found to be sensitive to Kombucha. According to the literature on Kombucha, acetic acid is considered to be responsible for the inhibitory effect toward a number of microbes tested, and this is also valid in the present study. However, in this study, Kombucha proved to exert antimicrobial activities against E. coli, Sh. sonnei, Sal. typhimurium, Sal. enteritidis, and Cm. jejuni, even at neutral pH and after thermal denaturation. This finding suggests the presence of antimicrobial compounds other than acetic acid and large proteins in Kombucha.


Effects of staff-patient relations training on employees and their feelings about their work.
This article describes a study in which 16 health care workers participated in a two-hour staff-patient relations training session that was held once weekly for three weeks. Training included discussions of empathy, anger, stress management, effective communication, managing irate or difficult patients and families empathetically, and the concept of "positive stroking." The participants were given a pretest and posttest of program content and they also completed a five-item Likert scale survey. The patients rated themselves as overall improved in five areas of self-evaluation. The scores were significantly improved in the posttest group. There was a high correlation between "before" and "after" scores.


Models of repression of transposition in P-M hybrid dysgenesis by P cytotype and by zygotically encoded repressor proteins.
By analytical theory and computer simulation the expected evolutionary dynamics of P transposable element spread in an infinite population are investigated. The analysis is based on the assumption that, unlike transposable elements which move via RNA intermediates, the harmful effects of P elements arise primarily in the act of transposition, and that this causes their evolutionary dynamics to be unusual. It is suggested that a situation of transposition-selection balance will be superceded by the buildup of a cytoplasmically inherited repression or by the elimination of active transposase-encoding elements from the chromosomes, a process which may be accompanied by the evolution of elements which encode proteins which repress transposition.


Glial fibrillary acidic protein immunoglobulin G as biomarker of autoimmune astrocytopathy: Analysis of 102 patients.
A novel autoimmune central nervous system (CNS) disorder with glial fibrillary acidic protein (GFAP)-IgG as biomarker was recently characterized. Here, 102 patients with GFAP-IgG positivity are described. The 102 included patients had: (1) serum, cerebrospinal fluid (CSF), or both that yielded a characteristic astrocytic pattern of mouse tissue immunostaining; (2) confirmation of IgG reactive with specific GFAP isoforms (α, ɛ, or κ) by cell-based assays; and (3) clinical data available. Control specimens (n = 865) were evaluated by tissue (n = 542) and cell-based (n = 323) assays. Median symptom onset age was 44 years (range = 8-103), and 54% were women. The predominant phenotype (83 patients; 81%) was inflammation of meninges, brain, spinal cord, or all 3 (meningoencephalomyelitis). Among patients, highest specificity for those phenotypes was observed for CSF testing (94%), and highest sensitivity was for the GFAPα isoform (100%). Rare GFAP-IgG positivity was encountered in serum controls by tissue-based assay (0.5%) or cell-based assay (1.5%), and in CSF controls by cell-based assay (0.9%). Among patients, striking perivascular radial enhancement was found on brain magnetic resonance imaging in 53%. Although cases frequently mimicked vasculitis, angiography was uniformly negative, and spinal imaging frequently demonstrated longitudinally extensive myelitic lesions. Diverse neoplasms encountered were found prospectively in 22%. Ovarian teratoma was most common and was predicted best when both N-methyl-D-aspartate receptor-IgG and aquaporin-4-IgG coexisted (71%). Six patients with prolonged follow-up had brisk corticosteroid response, but required additional immunosuppression to overcome steroid dependency. GFAPα-IgG, when detected in CSF, is highly specific for an immunotherapy-responsive autoimmune CNS disorder, sometimes with paraneoplastic cause. Ann Neurol 2017;81:298-309.


A prospective study of external stenting of saphenous vein grafts to the right coronary artery: the VEST II study.
External stents significantly reduce intimal hyperplasia and improve lumen uniformity and flow pattern in saphenous vein grafts (SVG) 1 year after coronary artery bypass grafting. However, recent studies have shown that at 1 year there is a lower patency of externally stented SVG to the right coronary artery (RCA) (55-60%) when compared to the left sided coronary arteries (85-90%). In the current study, we investigated whether avoidance of both fixation of the external stent to the anastomoses and the use of metal clips to ligate SVG side branches would improve the early patency of externally stented SVG to the RCA. Thirty patients received a SVG to the right territory supported with an external stent. Graft patency was confirmed at the end of surgery in all patients. The primary endpoint was SVG patency assessed by computed tomography angiography (CTA) at 3-6 months. Graft failure was defined as > 50% stenosis. Twenty-nine patients (96.6%) completed the follow up period and CT angiography data was available for a total of 43 SVGs, (29 supported and 14 unsupported SVGs) and 47 arterial grafts. Patency of stented SVGs was 86.2% (25/29 on CTA). All non-stented SVGs to the left territory were patent. Patency rates of the left internal mammary arteries and right internal mammary arteries grafts were 96.6% and 83.3%, respectively. Avoidance of both metallic clips to ligate side branches and of fixation of venous external support trial (VEST) stents to the anastomoses mark a significant improvement in patency of stented SVG to the right coronary territory.


[Risk factors for the recurrence of spinocellular epithelioma. Study of 650 cases].
An evaluation is made of the clinical and histological parameters of 650 cases of spinocellular epithelioma. The statistical analysis shows tumor relapse to be related to tumor size, evolution time, relapse following previous treatments, earlier cutaneous lesions, Broders' grading, acantholysis, inflammatory infiltrate and type of treatment applied.


[Ketamine as an anesthetic, analgesic and anti-depressant].
Treatment-resistance occurs in about 30% of patients with depression. Therefore, there is an urgent need to identify new treatment strategies. Ketamine, originally developed as an anesthetic, is studied and applied as treatment for patients with treatment-resistant depression.
 AIM: A critical review of the current use of ketamine as an antidepressant.
 METHOD: Literature study.
 RESULTS: Ketamine is a proven effective acute antidepressant. However, limited information is available about maintenance of effect of ketamine, potential risks of repeated administration, and different routes of administration and treatment schedules.
 CONCLUSION: Additional research on ketamine as an antidepressant is needed. Meanwhile, (off-label) treatment should only be applied after careful patient selection and under close monitoring.


Stress pulmonary circulation parameters assessed by a cardiovascular magnetic resonance in patients after a heart transplant.
Rest pulmonary circulation parameters such as pulmonary transit time (PTT), heart rate corrected PTT (PTTc) and pulmonary transit beats (PTB) can be evaluated using several methods, including the first-pass perfusion from cardiovascular magnetic resonance. As previously published, up to 58% of patients after HTx have diastolic dysfunction detectable only in stress conditions. By using adenosine stress perfusion images, stress analogues of the mentioned parameters can be assessed. By dividing stress to rest biomarkers, potential new ratio parameters (PTT ratio and PTTc ratio) can be obtained. The objectives were to (1) provide more evidence about stress pulmonary circulation biomarkers, (2) present stress to rest ratio parameters, and (3) assess these biomarkers in patients with presumed diastolic dysfunction after heart transplant (HTx) and in childhood cancer survivors (CCS) without any signs of diastolic dysfunction. In this retrospective study, 48 patients after HTx, divided into subgroups based on echocardiographic signs of diastolic dysfunction (41 without, 7 with) and 39 CCS were enrolled. PTT was defined as the difference between the onset time of the signal intensity increase in the left and the right ventricle. PTT in rest conditions were without significant differences when comparing the CCS and HTx subgroup without diastolic dysfunction (4.96 ± 0.93 s vs. 5.51 ± 1.14 s, p = 0.063) or with diastolic dysfunction (4.96 ± 0.93 s vs. 6.04 ± 1.13 s, p = 0.13). However, in stress conditions, both PTT and PTTc were significantly lower in the CCS group than in the HTx subgroups, (PTT: 3.76 ± 0.78 s vs. 4.82 ± 1.03 s, p < 0.001; 5.52 ± 1.56 s, p = 0.002). PTT ratio and PTTc ratio were below 1 in all groups. In conclusion, stress pulmonary circulation parameters obtained from CMR showed prolonged PTT and PTTc in HTx groups compared to CCS, which corresponds with the presumption of underlying diastolic dysfunction. The ratio parameters were less than 1.


Careful interpretation of the wound status is needed with use of antibiotic impregnated biodegradable synthetic pure calcium sulfate beads: Series of 39 cases.
Introduction: The use of antibiotic impregnated biodegradable synthetic high purity calcium sulfate (SHPCS) beads is frequently reported as they offer increased concentration of antibiotics locally, without need for removal. However some wound discharge following their use has been noted. The purpose of this study was to determine any correlation between wound discharge and infection remission. Methodology: Retrospective study of 39 cases of Osteoarticular infections from April 2013 to November 2016 in whom SHPCS beads were used. All patients underwent the standard staged protocol of aggressive debridement, deep tissue biopsy, implant removal where indicated and early soft tissue cover. SHPCS beads were used locally in the second stage combined with appropriate antibiotics based on tissue culture. All patients received systemic antibiotics for a period of 6 weeks and followed up for a minimum period of six months. The study analysed the patient demographics, etiology, surgical procedures, culture patterns, local antibiotics used, radiological status of beads, incidence and characteristics of wound discharge and outcome. Results: There were 25 cases of chronic osteomyelitis, eight infected non unions, three peri prosthetic joint infections, two soft tissue infections and one case of acute osteomyelitis. 17 of these infections were following osteosynthesis. The cultures were negative on eight occasions in seven patients. A total of 40 organisms were isolated in the other patients; commonest being Staphylococcus aureus (n=16) and E coli (n=7). SHPCS beads were mixed with vancomycin in 17 cases, colistin in 11, vancomycin with colistin in eight and vancomycin with gentamicin in four. Voriconazole was used in one case with fungal infection. Eight cases (20.51 %) developed discharge from the wound at an average of 6 days after inserting the beads. The discharge was serous with no foul smell in six and purulent in two inflamed wounds. Four cases underwent re-debridement; two cases with purulent discharge and subsequent positive cultures; two with serous discharge early in the series and no evidence of infection on re-exploration with negative cultures. The remaining four patients with serous wound discharge were observed without any further surgical intervention, with the discharge stopping spontaneously between 15 to 36 days post operatively. There was no correlation between antibiotic used and wound discharge. Radiographic analysis showed dissolution of all the beads at an average of 36 days in the 39 cases. Heterotrophic ossification was not observed. Clinical and radiological remission of infection was observed in 37 cases (94.9%). Two patients died during the course of hospitalization, secondary to septicaemia and multi organ failure. Three patients had an infection recurrence within six months, managed successfully by re-debridement and appropriate antibiotics. Radiological union was achieved in seven of the eight infected non unions. Conclusions: With the encouraging rates of infection remission we have observed, we continue to use antibiotic loaded SHPCS as an alternative for local antibiotic delivery in the treatment of osteoarticular infections. However, wound discharge is a known potential observation following implantation of calcium sulfate beads, subsiding typically within four to six weeks. The appearance of wound discharge can vary, ranging from purulent discharges to non-purulent, serous/ sero sanguineous fluid wound discharges. The presence of a wound discharge alone does not necessarily imply a failure to treat the infection. It is important to be aware of this side effect and guard against unnecessary re- operations, by careful consideration and monitoring all of the available clinical signs of infection, in addition to blood test results and radiographic evidence. Further research is needed to determine the relationship between the implantation of antibiotic loaded calcium sulfates and the incidence and duration of drainage.


Associations between drug use and motorcycle helmet use in fatal crashes.
Helmet use reduces mortality risk for motorcyclists, regardless of drug and alcohol use. However, the association between drug use and motorcycle helmet utilization is not well known. This study examines the relationship between drug use and motorcycle helmet use among fatally injured motorcycle riders. Using data from the 2005-2009 Fatality Analysis Reporting System (FARS), we examined the association between drug use and motorcycle helmet use in a multivariable logistic regression analysis of 9861 fatally injured motorcycle riders in the United States. For fatally injured motorcycle riders, use of alcohol, marijuana, or other drugs was associated with increased odds of not wearing a motorcycle helmet, controlling for the effects of state motorcycle helmet laws and other confounding variables. Predicted probabilities indicate that helmet use substantially decreases among fatally injured riders mixing alcohol with marijuana and other drugs. Furthermore, the likelihood of helmet use between marijuana-only users and other drug users is virtually the same across all blood alcohol content (BAC) levels. This study provides evidence that alcohol, marijuana, and other drug use is associated with not wearing a motorcycle helmet in fatal motorcycle crashes. There is a clear need for additional prevention and intervention efforts that seek to change helmet and drug use norms among motorcycle riders.


Efficient gene expression system using the RTP801 promoter in the corpus cavernosum of high-cholesterol diet-induced erectile dysfunction rats for gene therapy.
The application of gene therapy for a nonlife-threatening disease, such as erectile dysfunction (ED), requires a higher safety level and more efficacious systems for gene transfer. To establish a novel technique for gene expression in a rat model of hypercholesterolemic ED that uses the RTP801 promoter, a hypoxia-inducible promoter. Two-month-old male Sprague-Dawley rats were fed a diet containing 4% cholesterol and 1% cholic acid, and age-matched control animals were fed a normal diet, for 3 months. Cavernous expression of hypoxia-inducible factor (HIF)-1alpha was evaluated by Western blot. After intracavernous injection of pSV-Luc or pRTP801-Luc, gene expression was evaluated by luciferase assay, and the gene expression area was evaluated by immunohistochemistry. HIF-1alpha was up-regulated in the corpus cavernosum of hypercholesterolemic rats. Although pSV-Luc did not induce gene expression in either the control or the cholesterol group, pRTP801-Luc significantly induced gene expression in the cholesterol group and resulted in higher luciferase activity than did pSV-Luc up to 14 days after injection. Immunohistochemistry showed that the gene expression area was also greater in the pRTP801-Luc group than in the pSV-Luc group, but the difference was not as great as that in luciferase activity. This suggests that pRTP801-Luc exerts its effect mainly by inducing promoter activity under hypoxia, not by increasing the number of transfected cells. The RTP801 promoter-driven gene expression system increased gene expression in the corpus cavernosum tissue of rats with cholesterol-induced ED. This may be a useful system for the development of gene therapy in vasculogenic ED.


IDH1 Mutation Promotes Tumorigenesis by Inhibiting JNK Activation and Apoptosis Induced by Serum Starvation.
Two hallmarks of cancer cells are their resistance to apoptosis and ability to thrive despite reduced levels of vital serum components. c-jun N-terminal kinase (JNK) activation is crucial for apoptosis triggered by serum starvation (SS), and isocitrate dehydrogenase 1 (IDH1) mutations are tumorigenic, in part, because they produce the abnormal metabolite 2-hydroxyglutarate (2-HG). However, it is unknown whether 2-HG-induced tumorigenesis is partially due to JNK inhibition and thus defective SS-induced apoptosis. We show here, using IDH1-R132Q knockin mutant mouse cells, that 2-HG inhibits JNK activation induced only by SS and not by UV or doxorubicin, and thus can block apoptosis. Upon SS, Cdc42 normally disrupts mixed lineage kinase 3's (MLK3's) auto-inhibition, triggering the MLK3-MKK4/7-JNK-Bim apoptotic cascade. 2-HG binds to Cdc42 and abolishes its association with MLK3, inactivating MLK3 and apoptosis. Allograft tumor assays in mice demonstrate that this mechanism contributes to tumorigenesis driven by mutant IDH1, a result confirmed by detection of JNK inactivation in human gliomas harboring IDH1-R132H mutations.


Charcot-Marie-Tooth Disease 1X Simulating Paraparetic Guillain-Barre Syndrome.
X-linked Charcot-Marie-Tooth disease (CMT 1X) is the second most common form of inherited demyelinating neuropathy. It is established that patients suffering from CMT 1X can have episodes of hemiparesis, paraparesis, quadriparesis, ataxia, aphasia, and dysarthria, which can be fully reversible, and 'trigger' factors for these episodes are usually febrile illness, high altitudes, hyperventilation, and physical activity. We describe a 22-year-old patient with a history of viral infection and sleep deprivation who presented to our department because of acute difficulty in walking and neurophysiological findings suggesting Guillain-Barre syndrome. The patient's phenotype was compatible with CMT disease and within hours he showed remarkable improvement of his muscle strength without receiving any medical treatment. Any other metabolic, infectious, vasculitic, hematological, paraneoplastic, or infiltrative cause of polyneuropathy was excluded with laboratory work-up. Diagnosis of CMT 1X was confirmed with repeated neurophysiological study and genetic testing of his and his mother's blood, demonstrating the Arg75Trp [CGG to TGG,(R75W)] mutation on exon2 of gap junction protein beta 1. CMT 1X should be considered in patients with a phenotype compatible with the disease, rapid improvement of their clinical manifestations, and neurophysiological findings consistent with a hereditary, demyelinating neuropathy.


Influence of dietary fat on the nutrient intake and growth of children from 1 to 5 y of age: the Special Turku Coronary Risk Factor Intervention Project.
Excessive decreases in fat intake in young children have been linked with low intakes of energy and nutrients and possible growth failure. We evaluated nutrient intakes and growth of healthy children with different fat intakes during the first 5 y of life. In the Special Turku Coronary Risk Factor Intervention Project (STRIP), 7-mo-old children were randomly assigned to an intervention aimed at reduced consumption of saturated fat and cholesterol (n = 540) or to a control group (n = 522). This analysis comprises data for children for whom > or = 6 of 8 possible 3-4-d food records were available (n = 730; 353 females). Children were divided according to fat intake pattern (percentage of energy) between the ages of 13 mo and 5 y into groups with continuously high fat intake (5% of children), increasing fat intake (5%), continuously low fat intake (5%), decreasing fat intake (5%), and average fat intake (80%). Children's energy and nutrient intakes and growth were then compared by analysis of variance. Fat intake at 13 mo of age was particularly low (21% of energy) in the increasing fat intake group and in the continuously low fat intake group (22% of energy at 13 mo; 26% of energy at 5 y). Growth of children in all 5 fat intake groups, however, was not significantly different throughout the study period. Intakes of vitamins and minerals, except of vitamin D, met recommended dietary allowances in all fat intake groups. Nutrient intakes and growth were not significantly different in children whose fat intake patterns differed between 13 mo and 5 y of age.


Free fatty acids as a cardiovascular risk factor.
Free fatty acids (FFAs) serve as physiologically important energy substrates and their release from the adipose tissue by lipolysis is regulated according to the energy demands of the body. FFAs are increased in obese patients and contribute to type 2 diabetes, hepatic steatosis and several cardiovascular diseases. In patients with heart failure and acute coronary syndromes, elevated FFA levels are a consequence of an increased lipolysis due to a surge in catecholamines and natriuretic peptides. FFAs contribute to myocardial dysfunction and are proarrhythmic, and their oxidation requires more oxygen than does glycolysis. Therapeutic approaches have already emerged that aim to reduce the uptake and/or oxidation of fatty acids in the myocardium. The routine use of FFAs as a diagnostic tool is limited by their high variability, this being strongly influenced by nutrition and the effects of several hormones. In addition, it remains to be clarified whether fasting or postprandial values or dynamic measurements such as changes in FFA concentrations induced by stress are better parameters for evaluating cardiovascular risk. In this review, we present an overview of the metabolism and role of FFAs as a cardiovascular risk factor and discuss the potential of FFAs in the diagnosis and treatment of cardiovascular diseases.


Vascular biology of coronary bypass grafts.
Clinical studies on the natural history of coronary bypass grafts strongly suggest that biologic properties of the vessels used importantly affect their function and patency. The endothelium is a source of substances regulating vascular tone, platelet function, and vascular growth; it produces nitric acid from L-arginine, which is a potent vasodilator and inhibitor of platelet function and has antiproliferative properties. Nitric oxide and prostacyclin, which have a similar profile of action, are released in greater amounts in arterial than venous coronary bypass vessels. Vascular smooth muscle cells are primary regulators of local blood flow and contribute to proliferative responses. The right gastroepiploic artery exhibits more pronounced contractions than the mammary artery but has a similar sensitivity to vasoconstrictors. Proliferative responses in coronary bypass vessels appear to be induced by changes in transmural pressure (particularly in veins), endothelial damage, and in turn, local release of platelet-derived growth factors, low-density lipoproteins, and intrinsic characteristics of the blood vessels. Thus, biologic properties of the endothelium and vascular smooth muscle significantly contribute to the function and patency of coronary bypass grafts. While the mammary artery has near-ideal characteristics, the right gastroepiploic artery exhibits marked contractile responses and the saphenous vein has unsatisfactory antithrombotic properties and more pronounced proliferative responses.


Washing machine usage in remote aboriginal communities.
The use of washing machines was investigated in two remote Aboriginal communities in the Anangu Pitjantjatjara homelands. The aim was to look both at machine reliability and to investigate the health aspect of washing clothes. A total of 39 machines were inspected for wear and component reliability every three months over a one-year period. Of these, 10 machines were monitored in detail for water consumption, hours of use and cycles of operation. The machines monitored were Speed Queen model EA2011 (7 kg washing load) commercial units. The field survey results suggested a high rate of operation of the machines with an average of around 1,100 washing cycles per year (range 150 and 2,300 cycles per year). The results were compared with available figures for the average Australian household. A literature survey, to ascertain the health outcomes relating to washing clothes and bedding, confirmed that washing machines are efficient at removal of bacteria from clothes and bedding but suggested that recontamination of clothing after washing often negated the prior removal. High temperature washing (> 60 degrees C) appeared to be advantageous from a health perspective. With regards to larger organisms, while dust mites and body lice transmission between people would probably be decreased by washing clothes, scabies appeared to be mainly transmitted by body contact and thus transmission would be only marginally decreased by the use of washing machines.


[Synthesis and transformations of ethyl 1,4-dihydro-4-oxo(1)benzofuro(3,2-b)pyridine-3-carboxylic acid esters: new antibacterial agents].
The title compound 7 was synthesized from potassium 3-amino-[1]benzofuran-2-carboxylate (1) by Gould-Jacobs-reaction. The pyridone 7 reacted with ethyl iodide by N- and O-alkylation to give 9 and 10, while methyl iodide only yielded the N-methylpyridone 11. The 4-chloropyridine 15 was obtained by heating 7 in phosphoryl chloride. Alkaline saponification of the esters 7, 9-11 and 15 afforded the carboxylic acids 8, 12-14 and 16. The carbaldehydes 19 and 22 were prepared from the ethylesters 10 and 15 by boranate reduction to the carbinoles 17 and 20 followed by dehydrogenation with activated manganese dioxide. The aldehyde 22 reacted with beta-aminocrotonic acid esters to yield the 1,4 dihydropyridines (DHP) 23. The pyridines 24 were formed by chemical or electrochemical dehydrogenation of the DHP 23. The tetrazole 27 was accessible from the aldehyde 22 via the aldoxime 25 and the nitrile 26. The pyridone 7 reacted with tosylisocyanate to yield the 4-tosylaminopyridine 28, which after alkylation to form 29 followed by detosylation to give 30 and subsequent alkaline hydrolysis produced the 4-aminonicotinic acid 31. The investigation The N-ethylpyridone-3-carboxylic acid 12 showed antibacterial activity comparable to the reference substance nalidixic acid against Pseudomonas aeruginosa, Escherichia coli and Bacillus megaterium.


Allometry: revealing evolution's engineering principles.
An animal's body size impacts many aspects of its structure and function (Y); insights that only become apparent when viewed over several orders of magnitude of body mass (M) and expressed allometrically in the form of power law equations (Y=aMb). The resulting relationships are apparent clusters of similar exponents (b) revealing emergent 'patterns of design' that shed light on the universal principles of structure and function. Basic physical principles of surface area, volume and heat exchange apply to all objects, including animals, and many consequences must be attributed to these fundamental properties. Starting with Galileo's description of the shapes of bones in the 16th century and extending to 19th century explanations of heat production and loss by Sarrus and Rameaux, allometric patterns have provided numerous biological insights. Here, we examine several of these insights and explore how the selective pressures and scaling may differ when comparing animals in a vegetative (basal) state and those utilizing their maximum metabolic capacities. It seems that the selective pressures under those two conditions differ. We caution that allometric patterns invite explanations that lack supporting data or may be dismissed because there is hesitation among biologists to make comparisons lacking phylogenetic support. We argue that emergent allometric patterns have inherent value and continue to be the fodder for many fruitful hypotheses.


Recombinant immunotoxins for the treatment of Hodgkin's disease (Review).
In recent years, substantial experience has been accumulated with tumor-specific immunotherapeutics which seem to be effective against minimal residual disease. The coupling of toxins to monoclonal antibodies has indicated promising results in early clinical trials. Recombinant DNA technology makes it possible to genetically fuse coding regions of V genes or cytokines to modified toxin domains. These recombinant immunotoxins can easily be manipulated to increase the cytotoxic potency or affinity. Binding single-chain variable fragments (scFv) expressed as chimeric fusion proteins on the surface of filamentous bacteriophages were selected on Hodgkin-derived cell lines. This technique was also used to create a new humanized anti-CD30 scFv which exhibits similar binding to the CD30 antigen when compared to its murine predecessor. ScFvs were then inserted into a new bacterial expression vector and thus fused to a deletion mutant of Pseudomonas exotoxin. Anti-CD25(scFv)-ETA' and anti-CD30(scFv)-ETA' were isolated from E. coli periplasm and purified by metal chelate affinity and size exclusion chromatography. All immunotoxins produced showed specific cytotoxicity against Hodgkin lymphoma cell lines as documented by competitive assays. In addition, these constructs were highly efficient in the treatment of disseminated human Hodgkin's disease in SCID mice. These in vivo data indicate a possible clinical impact for patients with relapsed CD25- and/or CD30-positive lymphoma.


Measuring motivation to change in sexual offenders from institutional intake to community treatment.
Changes in motivational levels occurring during various stages of treatment (institutional and community) were measured among 101 federally sentenced sexual offenders in the Ontario region. Motivation was conceptualized as a dynamic process that can be construed from behavioral referents and more global evaluations of internal features/readiness/psychological stance. Five motivational indices were examined: acceptance of guilt for the offense; acceptance of personal responsibility for the offense; disclosure of personal information; motivation to change behavior; and participation in treatment. Offender scores on these indices were evaluated using the Goal Attainment Scaling protocol (T. Hogue, 1994), at four stages of the treatment process: (1) at institutional assessment, (2) following institutional treatment, (3) upon conditional release to the community, and (4) following a 12-week period of community treatment. Results showed that motivation to change sexually deviant behavior was higher at the end of institutional treatment relative to the initial assessment. However, levels of motivation decreased upon conditional release to the community, with few offenders making significant rebounds following 12 weeks of community treatment. Admission of guilt and acceptance of personal responsibility (measured at community treatment) were both significantly associated with treatment outcome.


A Scoping Review on Work Experiences of Nurses After Being Diagnosed With Cancer.
To map key concepts underpinning work-related studies about nurses with cancer and identify knowledge gaps. A search was conducted in the PubMed®, CINAHL®, and PsycINFO® databases for articles about nurses with cancer and work-related topics published through March 2023. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews Checklist was used to report results, and the JBI critical appraisal tools were used to assess the quality of studies. Eleven articles were included. The following four critical concepts were identified: role adjustments at work, cancer impacts on work, organizational support, and translating insights gained from cancer experience into work. Research gaps identified by the scoping review were a lack of theoretical or conceptual frameworks, lack of syntheses of main ideas, and lack of clear data about participants' socioeconomic status across studies. Minimal research exists to map predictors, outcomes, or intervention targets to guide organizational strategies to support nurses' retention in the nursing workforce. A guiding framework, recruitment of diverse nurses, and focus on the four critical concepts identified in this scoping review are suggested for future research.


Validation of Test Weighing Protocol to Estimate Enteral Feeding Volumes in Preterm Infants.
To evaluate the accuracy of pre- and postfeeding weights to estimate enteral feeding volumes in preterm infants. Single-center prospective cohort study of infants 28-36 weeks' corrected age receiving gavage feedings. For each test weight, 3 pre- and 3 postgavage feeding weights were obtained by study personnel, blinded to feeding volume, via a specific protocol. The correlation between test weight difference and actual volume ingested was assessed by the use of summary statistics, Spearman rho, and graphical analyses. The relationship between categorical predictive variables and a predefined acceptable difference (±5 mL) was assessed with the χ2 or Fisher exact test. A total of 101 test weights were performed in 68 infants. Estimated and actual feeding volumes were highly correlated (r = 0.94, P < .001), with a mean absolute difference of 2.95 mL (SD: 2.70; range: 0, 12.3 mL; 5th, 95th percentile: 0, 9.3); 85% of test weights were within ±5 mL of actual feeding volume and did not vary significantly by corrected age, feeding tube or respiratory support type, feeding duration or volume, formula vs breast milk, or caloric density. With adherence to study protocol, 89% of test weights (66/74) were within ±5 mL of actual volume, compared with 71% (19/27, P = .04) when concerns about protocol adherence were noted (eg, difficulty securing oxygen tubing). Via the use of a standard protocol, feeding volumes can be estimated accurately by pre- and postfeeding weights. Test weighing could be a valuable tool to support direct breastfeeding in the neonatal intensive care unit.


Statistical Shape Analysis of Cerebellum in Patients With Chiari Malformation I.
The surgical procedure is viewed as a typical treatment choice for patients with Chiari malformation (CM). Decompression is the preferred method for surgery, but it is not always possible to understand whether decompression has been successful especially in an early period. The present study focuses on investigating the shape differences in the cerebellums of Chiari patients compared with healthy controls, and to assess the clinical application of this situation whether if present. The MRI scans were reviewed retrospectively. Cerebellar data were obtained from the digital images and 9 anthropometric landmarks were marked on each image. Shape difference was assessed by performing Generalized Procrustes analysis. The cerebellar shape deformation from control to the patient was evaluated performing the Thin Plate Spline approach. There is a statistically significant cerebellar shape difference between groups. Highest deformation was determined at the cerebellar tonsillar inferior area, posterior of the uvula, and anterior of inferior medullary velum. The present study demonstrated cerebellar shape differences in CM I patients using a landmark-based geometric morphometric approach, considering the topographic distribution of cerebellum for the first time.


Parallel signaling pathways in endothelin-1-induced proliferation of U373MG astrocytoma cells.
Endothelin-1 (ET-1) is a potent mitogen for many cells, especially when its levels are elevated under pathological conditions, as seen in tumor cell progression and astroglial activation in neuropathies. While ET-1 is known to cause astroglial proliferation, in the present study, multiple signaling pathways involved in ET-1-mediated astrocyte proliferation were characterized. Treatment with PD98059 and U0126 (MEK inhibitors) inhibited not only ET-1-induced cell proliferation but also ET-1-activated phosphorylation of extracellular signal-regulated protein kinase 1/2 (ERK1/2) in U373MG astrocytoma cells. Whereas the nonselective protein kinase C (PKC) inhibitor chelerythrine attenuated ET-1-induced cell proliferation, it was unable to block ET-1-induced ERK phosphorylation. However, ET-1 did not activate conventional or novel PKCs and did not elevate intracellular calcium. In addition, U73122 (a selective phospholipase C inhibitor), FTI-277 (an H-Ras inhibitor), as well as protein tyrosine kinase inhibitors also did not abolish ET-1-induced ERK1/2 phosphorylation. ET-1 treatment increased the activity of total Ras but not H-Ras. The phosphoinositide 3-kinase (PI3K) pathway appeared to be involved in signal transduction induced by ET-1, but it did not appear to participate in cross talk with the mitogen-activated protein kinase (MAPK) pathway. Activated ET receptors did not propagate signals either through protein tyrosine kinases or transactivation of EGF receptor tyrosine kinases, which typically trigger Ras-Raf-MAPK pathways. The results indicate that ET-1 stimulates cell proliferation by the activation of MAPK-, PKC-, and PI3K-dependent pathways that appear to function in a parallel manner. There is no apparent, direct "cross talk" between these pathways in U373MG cells, but rather, they might act on the independent but necessary components of the mitogenic effects of ET-1.


Early and late responses in patients with rheumatoid arthritis who were conventional synthetic disease-modifying anti-rheumatic drug inadequate responders and were treated with tocilizumab or switched to rituximab: an open-label phase 3 trial (MIRAI).
To evaluate early and late responses in biological-naïve patients with rheumatoid arthritis (RA) initiating tocilizumab and early tocilizumab non-responders who switched to rituximab. In this open-label, non-randomised phase 3 study, RA patients with inadequate response to conventional synthetic DMARDs received tocilizumab 8 mg/kg intravenously at study begin and weeks 4, 8 and 12. After evaluation at week 16, early responders (Disease Activity Score based on 28 joints-erythrocyte sedimentation rate [DAS28-ESR] <2.6) completed the study; partial responders (DAS28-ESR decrease >1.2 or DAS28-ESR ≥2.6-≤3.2) were to continue tocilizumab through week 28; non-responders (DAS28-ESR decrease ≤1.2) switched to rituximab (1000 mg, weeks 16 and 18) with safety follow-up through week 66. Of 519 patients, 222 (42.8%) achieved early DAS28-ESR remission at week 16; 240 patients continued treatment, 213 (41.0%) received tocilizumab, and 27 (5.2%) switched to rituximab. At week 32 DAS28-ESR remission was achieved by 117/213 patients (54.9%) who continued tocilizumab and 4/27 patients (14.8%) who switched to rituximab; good EULAR response was achieved by 66.7% and 25.9% and CDAI remission by 19.2% and 14.8% of patients, respectively. Serious adverse events occurred through week 32 in 45/490 patients (9.2%) who received tocilizumab (serious infections, 2.7%) and through week 66 in 8/27 patients (29.6%) who switched to rituximab. Early response to tocilizumab was observed in 42.8% of patients. Half of early partial responders benefitted from continuing tocilizumab. Switching non-responders to rituximab seems feasible. No new safety signals were observed in patients treated with tocilizumab or switched to rituximab.


Loss of hepatic DEPTOR alters the metabolic transition to fasting.
The mechanistic target of rapamycin (mTOR) is a serine/threonine kinase that functions into distinct protein complexes (mTORC1 and mTORC2) that regulates growth and metabolism. DEP-domain containing mTOR-interacting protein (DEPTOR) is part of these complexes and is known to reduce their activity. Whether DEPTOR loss affects metabolism and organismal growth in vivo has never been tested. We have generated a conditional transgenic mouse allowing the tissue-specific deletion of DEPTOR. This model was crossed with CMV-cre mice or Albumin-cre mice to generate either whole-body or liver-specific DEPTOR knockout (KO) mice. Whole-body DEPTOR KO mice are viable, fertile, normal in size, and do not display any gross physical and metabolic abnormalities. To circumvent possible compensatory mechanisms linked to the early and systemic loss of DEPTOR, we have deleted DEPTOR specifically in the liver, a tissue in which DEPTOR protein is expressed and affected in response to mTOR activation. Liver-specific DEPTOR null mice showed a reduction in circulating glucose upon fasting versus control mice. This effect was not associated with change in hepatic gluconeogenesis potential but was linked to a sustained reduction in circulating glucose during insulin tolerance tests. In addition to the reduction in glycemia, liver-specific DEPTOR KO mice had reduced hepatic glycogen content when fasted. We showed that loss of DEPTOR cell-autonomously increased oxidative metabolism in hepatocytes, an effect associated with increased cytochrome c expression but independent of changes in mitochondrial content or in the expression of genes controlling oxidative metabolism. We found that liver-specific DEPTOR KO mice showed sustained mTORC1 activation upon fasting, and that acute treatment with rapamycin was sufficient to normalize glycemia in these mice. We propose a model in which hepatic DEPTOR accelerates the inhibition of mTORC1 during the transition to fasting to adjust metabolism to the nutritional status.


A study on screening of osteosarcoma U2OS cell inhibiting active components from nidus vespae.
This paper mainly examined the anti-osteosarcoma activity of total flavonoids extract from traditional Chinese medicine, nidus vespae. Orthogonal design was used to design the extraction process of total flavonoids. L(3(4)) orthogonal test was performed and the extracts obtained by three optimal extraction processes were used for anti-tumour activity screening in order to determine the optimal anti-tumour effective component of nidus vespae. MTT assay was used to investigate the effect of nidus vespae extract on proliferation activity of osteosarcoma cells. Meanwhile, U2OS cell inhibitory capacities of extracts in three groups with higher total flavonoid contents were investigated and compared, and inhibition rates were calculated. The results showed that the optimal extraction process was ethanol concentration of 95%, 12-fold amount of ethanol relative to the weight of medicinal material, extraction times of 3 times, and extraction time of 2 hours. 9 extraction processes all showed proportional trend of cancer cell inhibition rate to extract concentration.


Morphological traits defining species differences in wild relatives of maize are controlled by multiple quantitative trait loci.
We analyzed the genetic basis of morphological differences between two wild species of teosinte (Zea diploperennis and Z. mays ssp. parviglumis), which are relatives of maize. These two species differ in a number of taxonomically important traits including the structure of the tassel (male inflorescence), which is the focus of this report. To investigate the genetic inheritance of six tassel traits, quantitative trait locus (QTL) mapping with 95 RFLP markers was employed on a population of 425 F2 plants. Each trait was analyzed by interval mapping (IM) and composite interval mapping (CIM) to identify and characterize the QTL controlling the differences in tassel morphology. We detected two to eight QTL for each trait. In total, 30 QTL with IM and 33 QTL with CIM were found for tassel morphology. QTL for several of the traits mapped near each other, suggesting pleiotropy and/or linkage of QTL. The QTL showed small to moderate magnitudes of effect. No QTL of exceptionally large effect were found as seen under domestication and in the case of some other natural species. Thus, the model involving major QTL of large effect seems not to apply to the traits and species analyzed. A mixture of QTL with positive and negative allelic effects was found for most tassel traits and may suggest a history of periodic changes in the direction of selection during the divergence of Z. diploperennis and Z. mays ssp. parviglumis or fixation of QTL alleles by random genetic drift rather than selection.


Oxidative stress is associated with an increased antioxidant defense in elderly subjects: a multilevel approach.
Studies of associations between plasma GSH-Px activity and cardiovascular risk factors have been done in humans, and contradictory results have been reported. The aim of our study was to assess the association between the scavenger antioxidant enzyme glutathione peroxidase (GSH-Px) activity in plasma and the presence of novel and classical cardiovascular risk factors in elderly patients. We performed a cross-sectional study with baseline data from a subsample of the PREDIMED (PREvención con DIeta MEDiterránea) study in Spain. Participants were 1,060 asymptomatic subjects at high risk for cardiovascular disease (CVD), aged 55 to 80, selected from 8 primary health care centers (PHCCs). We assessed classical CVD risk factors, plasma oxidized low-density lipoproteins (ox-LDL), and glutathione peroxidase (GSH-Px) using multilevel statistical procedures. Mean GSH-Px value was 612 U/L (SE: 12 U/L), with variation between PHCCs ranging from 549 to 674 U/L (Variance = 013.5; P<0.001). Between-participants variability within a PHCC accounted for 89% of the total variation. Both glucose and oxidized LDL were positively associated with GSH-Px activity after adjustment for possible confounder variables (P = 0.03 and P = 0.01, respectively). In a population at high cardiovascular risk, a positive linear association was observed between plasma GSH-Px activity and both glucose and ox-LDL levels. The high GSH-Px activity observed when an oxidative stress situation occurred, such as hyperglycemia and lipid oxidative damage, could be interpreted as a healthy defensive response against oxidative injury in our cardiovascular risk population.


A novel dense granule protein, GRA41, regulates timing of egress and calcium sensitivity in Toxoplasma gondii.
Toxoplasma gondii is an obligate intracellular apicomplexan parasite with high seroprevalence in humans. Repeated lytic cycles of invasion, replication, and egress drive both the propagation and the virulence of this parasite. Key steps in this cycle, including invasion and egress, depend on tightly regulated calcium fluxes and, although many of the calcium-dependent effectors have been identified, the factors that detect and regulate the calcium fluxes are mostly unknown. To address this knowledge gap, we used a forward genetic approach to isolate mutants resistant to extracellular exposure to the calcium ionophore A23187. Through whole genome sequencing and complementation, we have determined that a nonsense mutation in a previously uncharacterised protein is responsible for the ionophore resistance of one of the mutants. The complete loss of this protein recapitulates the resistance phenotype and importantly shows defects in calcium regulation and in the timing of egress. The affected protein, GRA41, localises to the dense granules and is secreted into the parasitophorous vacuole where it associates with the tubulovesicular network. Our findings support a connection between the tubulovesicular network and ion homeostasis within the parasite, and thus a novel role for the vacuole of this important pathogen.


[Appendicitis during pregnancy].
Acute appendicitis es the most common cause of lapparotomy during pregnancy. The differential diagnosis in the pregnant woman becomes a challenge due to the anatomic changes that take place during the maternal adjustment to pregnancy. We have done a retrospective study between january 1989 and december 1994, at Instituto Nacional de Perinatologia. We found in that period of time 35,080 deliveries reported and 4 cases of acute appendicitis during pregnancy. The maternal age was between 16 and 42 years old, 26 years in average. Three patients were in the 3 trimester at the time of diagnosis, and the most important clinical sign was found to be diffuse abdominal pain. In 3 cases diagnosis was attributed to obstetric pathology rather than appendicitis in first place. Laparotomy and appendicectomy was done to all patients, with on block hysterectomy in only one case, having this particular patient an abscess as a postquirurgical complication. Just one case reported a healthy newborn delivered at term. It is obvious that early diagnosis and quirurgical treatment are important factors for the mother and the fetus prognosis. Appendicectomy as well as cholecystectomy are the two most common causes of laparotomy during pregnancy.


The interactive effects of chytrid fungus, pesticides, and exposure timing on gray treefrog (Hyla versicolor) larvae.
Aquatic organisms are often exposed to a wide variety of perturbations in nature, including pathogens and chemical contaminants. Despite the co-occurrence of these 2 stressors, few studies have examined the effects of chemical contaminants on host-pathogen dynamics. The authors tested the individual and combined effects on gray treefrog (Hyla versicolor) tadpoles of 2 commonly used pesticides (Roundup® and Sevin®) and the pathogenic fungus Batrachochytrium dendrobatidis (Bd). A fully factorial design was used, and tadpoles were exposed to Bd, Roundup, or Sevin alone, or a combination of Bd and either pesticide at 3 points during larval development (early, mid, late). It was predicted that pesticides would mediate the effect of Bd on tadpoles and reduce the likelihood of negative consequences of infection and that timing of exposure would influence these effects. Tadpoles exposed to Bd at the mid point experienced higher survival through metamorphosis than those exposed to Bd at the early or late points, while tadpoles exposed to Sevin at the early point experienced reduced survival compared with those exposed to Roundup or no-pesticide control at the same exposure point. Roundup ameliorated the effects of Bd on survival compared with tadpoles exposed to Bd alone, while there was no interactive effect of Sevin on survival. In addition, Sevin reduced mass of new metamorphs compared with Roundup and reduced snout-vent length compared with all other treatments. The present study supports the hypothesis that pesticides can mitigate the effects of Bd on amphibian hosts and that such effects may depend on the timing of exposure.


Management characteristics of successful public health programs: "Avahan" HIV prevention program in India.
This paper analyzes Avahan, an HIV prevention program in India, that achieved very rapid scale-up. The paper aims to (i) define the distinctive features of the management of Avahan, (ii) examine how the distinctive features relate to key constructs in management frameworks and (iii) investigate how the management approaches of Avahan contributed to the program's ability to scale-up rapidly while maintaining service quality. The Delphi method was used to identify the distinctive features of Avahan. Through three rounds of questions, 38 participants closely associated with Avahan were asked to identify and develop consensus on its distinctive features. These features were then mapped against the Baldrige Health Care Criteria for Performance Excellence to investigate how they related to important dimensions of management. A total of 17 distinctive features of Avahan were identified. These distinctive features emphasized the importance of data use and performance monitoring at all levels, especially combined with a flexible management style that facilitated local responsiveness to community, innovation and learning. The distinctive features comprehensively addressed the criteria for management excellence in the Baldridge framework. In the case of Avahan, the rigorous application of known management techniques to public health programs appears to have been an important factor in the successful scale-up of the program. Also, the Baldrige criteria seem applicable to health programs in low-income and middle-income countries; further applications would help test their robustness and utility in such contexts.