A Qualitative Analysis of First-Hand Accounts of Diphenhydramine Misuse Available on YouTube.
Deliriants are the least studied class of hallucinogens and display noticeable subjective effects, including dysphoria, hallucinations, and substantial alterations in thought. High doses of diphenhydramine (DPH), an over-the-counter antihistamine medication, can produce deliriant effects due to secondary anticholinergic activity. We sought to characterize the subjective experiences produced by DPH misuse to better understand deliriants more broadly and the context under which DPH misuse occurs. To conduct our analysis, 32 first-hand accounts of DPH misuse publicly available in YouTube videos were analyzed using inductive thematic analysis. Video makers discussed alterations in most sensory modalities, confusion, and a tendency for strongly unpleasant experiences. Occasionally, video makers reported positive effects, although these were rare and often overshadowed by negative aspects of the experience. Video makers frequently warned against misusing DPH, and these individuals occasionally reported adverse post-acute effects. Despite the prevalence of adverse experiences, patterns of repeated misuse were sometimes discussed. Motives for misusing DPH, when mentioned, included accessibility, affordability, and legality. Overall, findings suggest DPH misuse can produce substantial psychoactive effects that are often distressing and share some phenomenological overlap with experiences produced by psychosis.


How much the Iranian government spent on disasters in the last 100 years? A critical policy analysis.
During the past 20 years, Iran has been experiencing a significant increase in the occurrence of disasters mainly due to the emergence of anthropogenic climate change. This paper aims at analyzing the trend of national budget allocation in Iran over the last 100 years to evaluate the focus of the Iranian state on the four phases of Preparedness, Mitigation, Response, and Recovery and propose modifications. It is used a critical policy analysis with what's the problem represented approach. In this approach is focused on problematization and policy gaps. The most important policy statement in any government is the budget. During the first screening, 1028 regulations and laws were found from 1910 to 2020. After full text screening, 494 regulations and laws related to budget allocation to disasters were analyzed. The Iranian government has spent around 29 billion USD on disasters during the last 100 years. Droughts, earthquake and flood have costs the government more than other disasters, accounting for more than 14, 6.9, and 6.1 billion USD, respectively, in the allocated budget. Most of the Iranian government expenditure during the last 100 years on various disasters such as drought, flood, earthquake, and COVID-19 has been spent on involuntary costs including Response and Recovery. Mitigation and Preparedness are the two critical disaster management phases with very small shares of national budgeting. From policy audit and policy gaps it is concluded that Iranian governments during last 100 years, problematized the issue of "disasters strike" and not "disasters' risks". In time of disasters, governments tried to solve the issues or impacts of disasters with budgeting to response and recovery. Nevertheless, disasters' prevention or mitigation or preparedness was not a problem for Iranian governments from 1920 to 2020.


Idiopathic pulmonary fibrosis in asbestos-exposed workers.
Diffuse interstitial lung disease in asbestos-exposed workers is presumed to represent asbestosis. Among 176 asbestos-exposed persons for whom lung tissue was available, we found nine with clinical features consistent with asbestosis, but histologic sections failed to demonstrate asbestos bodies, the usual requirement for pathologic diagnosis of asbestosis (Group I). These nine were compared by analytic electron microscopy with nine persons with idiopathic pulmonary fibrosis (Group II), and with nine persons with all the criteria of asbestosis (Group III). The three groups did not differ significantly with respect to lung burden of chrysotile or tremolite and actinolite, but Group III had a lung burden of amosite and crocidolite that was three orders of magnitude greater than in Groups I and II, with no overlap. We conclude that (1) the American Thoracic Society criterion of "a reliable history of exposure" is sometimes difficult to define; (2) asbestos bodies are seen in tissue sections only when exposure has been reasonably high, and given the proper clinical setting, the presence of diffuse fibrosis and asbestos bodies in tissue sections are sensitive and specific criteria for a diagnosis of asbestosis; and (3) the prevalence here of 5.1% nonasbestos-induced interstitial lung disease among asbestos-exposed persons is artefactually high because of atypical case selection. However, because asbestosis is a disappearing disease, such cases will become more frequent. The identification of these other diseases is important because therapy and prognosis may differ from that of asbestosis.


Analysis of the behaviour of erythrocytes in an optical trapping system.
We present a theoretical analysis of the behaviour of erythrocytes in an optical trapping system. We modeled erythrocyte behaviour in an optical trap by an algorithm which divided the cell surface into a large number of elements and recursively summed the force and torque on each element. We present a relationship between the torque and angle of orientation of the cell, showing that stable equilibrium orientations are at angles of 0 o , 180 o and 360 o and unstable equilibrium orientations are at 90 o and 270 o relative to the axis of beam propagation. This is consistent with our experimental observations and with results described in the literature. We also model behaviour of the erythrocyte during micromanipulation by calculating the net force on it. Such theoretical analysis is practical as it allows for the optimization of the optical parameters of a trapping system prior to performing a specific optical micromanipulation application, such as cell sorting or construction of a cell pattern for lab-on-a-chip applications.


Retirement preparation programs: differentials in opportunity and use.
Two issues rarely addressed in the retirement planning field are (a) the proportion of older workers who participate, or have the opportunity to participate, in retirement preparation programs; and (b) socioeconomic differentials in access to such programs. Data from the National Longitudinal Surveys of older men were used to investigate these two issues. The data indicate that fewer than 4% of this sample of men aged 60 to 74 in 1981 had participated in a retirement preparation program. Logistic multiple regression analysis indicated that level of education, occupational status, government employment, and private pension coverage were positively related to the likelihood of participation as well as the likelihood of opportunity to participate. Conclusions from this analysis are (a) very few older men are ever exposed to retirement preparation programs and (b) those who would seem to benefit most from preparation programs, low status and low income workers, are the least likely to have access to these programs.


Surgical treatment of supracondylar humerus fractures in children.
Surgical techniques for the treatment of supracondylar fractures in children are repeatedly the subject of discussion. The aim of the present study was to compare experience with the technique of crossed Kirschner wires at our own hospital with current literature. In the period from 2000-2006 a total of 86 children aged 1.7 to 12.7 years were treated by means of crossed K-wire osteosynthesis. Follow up was conducted at an average of 32 months. Outcomes were evaluated based on von Laer's criteria. Reported complications were migration of the K-wires in 7% of cases and secondary dislocation and re-operation in 4% of cases. Lesion of the radial nerve was diagnosed postoperatively in two cases. Hospital stay was 1.5 days on average. Postoperative immobilization in an upper arm splint and implant removal after 6 weeks on average. 57% of the children received physiotherapy during the course of treatment. Slight varization was found in 11% of children and an unsatisfactory range of motion in 13%. Satisfactory outcomes were recorded for 83% of patients. K-wire osteosynthesis is associated with a low complication rate and continues to be a safe standard procedure for the stabilization of supracondylar humerus fractures. Key words: supracondylar humerus fracture, Kirschner wires, paediatric fractures.


Insights into the genetic diversity of Mycobacterium tuberculosis in Tanzania.
Human tuberculosis (TB) is caused by seven phylogenetic lineages of the Mycobacterium tuberculosis complex (MTBC), Lineage 1-7. Recent advances in rapid genotyping of MTBC based on single nucleotide polymorphisms (SNP), allow for phylogenetically robust strain classification, paving the way for defining genotype-phenotype relationships in clinical settings. Such studies have revealed that, in addition to host and environmental factors, strain variation in the MTBC influences the outcome of TB infection and disease. In Tanzania, such molecular epidemiological studies of TB however are scarce in spite of a high TB burden. Here we used SNP-typing to characterize a nationwide collection of 2,039 MTBC clinical isolates representative of 1.6% of all new and retreatment TB cases notified in Tanzania during 2012 and 2013. Four lineages, namely Lineage 1-4 were identified within the study population. The distribution and frequency of these lineages varied across regions but overall, Lineage 4 was the most frequent (n = 866, 42.5%), followed by Lineage 3 (n = 681, 33.4%) and 1 (n = 336, 16.5%), with Lineage 2 being the least frequent (n = 92, 4.5%). We found Lineage 2 to be independently associated with female sex (adjusted odds ratio [aOR] 2.14; 95% confidence interval [95% CI] 1.31 - 3.50, p = 0.002) and retreatment cases (aOR 1.67; 95% CI 0.95 - 2.84, p = 0. 065) in the study population. We found no associations between MTBC lineage and patient age or HIV status. Our sublineage typing based on spacer oligotyping on a subset of Lineage 1, 3 and 4 strains revealed the presence of mainly EAI, CAS and LAM families. Finally, we detected low levels of multidrug resistant isolates among a subset of 144 retreatment cases. This study provides novel insights into the MTBC lineages and the possible influence of pathogen-related factors on the TB epidemic in Tanzania.


Evaluation of amalgam-related retinal neurotoxicity with optical coherence tomography findings.
To evaluate the neurotoxic effect of amalgam dental fillings on plasma mercury (Hg) levels and retino-choroidal layers measured by spectral domain optical coherence tomography (SD-OCT). Study participants included 56 cases with amalgam dental fillings and 44 healthy controls. All participants were examined in terms of detailed ophthalmic examination, oral examination, and body mass index (BMI). The measurement of retinal layers and choroid was performed using SD-OCT. Venous blood samples were collected and blood Hg levels were measured using cold vapor atomic absorption spectrometric analysis. Correlations between SD-OCT measurement results and blood Hg levels were analyzed. There were no differences between groups in terms of age, sex, or BMI. The mean blood Hg level was 2.76 ± 1.21 µg/L in the amalgam group and 2.06 ± 1.15 µg/L in the control group ( p = 0.04). The Hg/BMI ratio was 0.12 ± 0.06 kg/m2 in the amalgam group and 0.09 ± 0.05 kg/m2 in the control group ( p = 0.01). Reduced volumes of ganglion cell layer and inner plexiform layer were observed in the amalgam group when compared with the control group ( p < 0.05). Amalgam dental fillings can cause retinal neurotoxicity. SD-OCT can be useful for evaluating amalgam-related retinal neurotoxicity.


Dealing with AIDS-related loss and grief in a time of treatment advances.
Recent advances in the treatment of HIV/AIDS have dramatically changed the lives of many patients and their loved ones as well as those who care for them. However, not all patients respond successfully to the latest treatments. Hospice professionals need to understand the experience of AIDS patients and their loved ones in this period of hope and disappointment, and to find appropriate ways to support and care for them. This article explores the implications of treatment advances for AIDS patients, their loved ones, and professionals in dealing with loss and grief.


Purified inositol hexakisphosphate kinase is an ATP synthase: diphosphoinositol pentakisphosphate as a high-energy phosphate donor.
Diphosphoinositol pentakisphosphate (PP-IP5) and bis(diphospho)inositol tetrakisphosphate (bis-PP-IP4) are recently identified inositol phosphates that possess pyrophosphate bonds. We have purified an inositol hexakisphosphate (IP6) kinase from rat brain supernatants. The pure protein, a monomer of 54 kDa, displays high affinity (Km = 0.7 microM) and selectivity for inositol hexakisphosphate as substrate. It can be dissociated from bis(diphospho)inositol tetrakisphosphate synthetic activity. The purified enzyme transfers a phosphate from PP-IP5 to ADP to form ATP. This ATP synthase activity indicates the high phosphate group transfer potential of PP-IP5 and may represent a physiological role for PP-IP5.


Gadolinium-based balloon angioplasty for pulmonary artery stenosis in an infant with a right isomerism.
We report here the first described case of utilizing gadolinium-based contrast material as the contrast agent during a catheter intervention treatment for pulmonary artery stenosis. The patient, a male infant with complex heart disease associated with a right isomerism, had a history of severe allergic reaction to iodine-containing contrast agents. A combination of digital subtraction angiography and a gadolinium contrast agent, however, provided us with good-quality images both before and after balloon angioplasty without any associated complications. This method should therefore be considered as an alternative angiographic procedure in children with a high risk of iodine-related allergic complications.


Communication in the time of COVID.
The risk of infection precluded normal visiting by relatives of COVID-19 patients in an intensive therapy unit (ITU). Instead, a team of medical students and retired consultants telephoned next of kin with a daily update. A categorised selection of the students' reflections on their experiences is presented and discussed.


Causes and consequences of obesity: the contribution of recent twin studies.
Obesity is a genetically complex disorder that produces a myriad of health problems. Most of the recognized complications of obesity are not only strongly influenced by lifestyle factors, but also present with independent genetic predispositions that are notoriously difficult to disentangle in humans. Most studies on the causes and consequences of acquired obesity are encumbered by the incomplete ability to control for genetic influences. However, utilizing a unique experiment of nature, namely monozygotic twins (MZ) discordant for obesity as 'clonal controls' of obese and non-obese individuals has enabled the fine characterization of the effects and possible antecedents of acquired obesity while controlling for the genetic background, as well as pointed to novel obesity predisposing candidate genes. This review is a distillation of the findings from more than 10 years of research done in an exceptionally well-characterized collection of MZ and dizygotic (DZ) twins, based on the Finnish Twin Cohorts. Topics covered include the nature of development of obesity from the childhood onwards, the role of exercise in modifying the genetic susceptibility, the resulting inflammatory, prediabetic and preatherosclerotic changes in whole body and adipose tissue physiology, as well as the newest insights provided by the omics revolution.


Elevated expression of interleukin-9 mRNA in the bronchial mucosa of atopic asthmatics and allergen-induced cutaneous late-phase reaction: relationships to eosinophils, mast cells and T lymphocytes.
Interleukin-9 is a T cell-derived Th2-type cytokine that has been linked to airway hyper-responsiveness, mucus hypersecretion and mast cell infiltration in animal models. We recently demonstrated the potential for IL-9 to act in human eosinophil development and survival. The aims of this study were: (i) to compare IL-9 mRNA expression in bronchial biopsies between atopic asthmatics and normal controls, (ii) to investigate kinetic expression of IL-9 mRNA in skin biopsies after allergen challenge; and (iii) to relate IL-9 expression to infiltration of eosinophils, mast cell and T lymphocytes in local tissue. Bronchial biopsies were obtained from atopic asthmatics (n = 12) and normal non-asthmatics (n = 12) at baseline. Skin biopsies were obtained from atopic subjects (n = 11) at 1, 3, 6, 24, 48 and 72 h after allergen challenge. Diluent challenge sites at 24 h were used as controls. IL-9 mRNA was identified using the technique of in situ hybridization. The numbers of eosinophils, mast cells and T cells were evaluated by immunohistochemistry. The numbers of IL-9 mRNA(+) cells present in the bronchial mucosa were significantly greater in atopic asthmatics than those in normal controls (P = 0.003). The numbers of eosinophils, but not mast cells, were also significantly higher in asthmatics (P < 0.005). The numbers of IL-9 mRNA(+) cells present in the airway of asthmatics significantly correlated with the numbers of eosinophils (r = 0.623, P = 0.03), but not mast cells or T cells. Compared with diluent challenge, the numbers of IL-9 mRNA(+) cells were significantly elevated at all allergen-challenged sites in the skin, with maximal signals at 48 h (P < 0.005). At 72 h, the numbers of IL-9 mRNA(+) cells significantly correlated with the numbers of eosinophils (r = 0.707, P = 0.015). Elevated expression of IL-9 in allergic inflammation may contribute to local eosinophil infiltration and survival in asthma and other allergic atopic diseases.


Does iron therapy benefit children with severe malaria-associated anaemia? A clinical trial with 12 weeks supplementation of oral iron in young children from the Turiani Division, Tanzania.
Oral iron supplementation is often routinely given to children with malaria-associated anaemia, but its contribution to recovery is controversial. A randomized clinical trial, evaluating such routine, was carried out among 100 children, who had a haemoglobin of < or = 5 g/dl and a positive blood smear for malaria parasites. All children received malaria therapy (chloroquin + fansidar) and were randomly allocated to two groups, one receiving additional oral iron treatment, the other being the control. In the 12-week follow-up period the haemoglobin level and malaria indices were measured at 2, 4, 8, and 12 weeks. There was a 100 per cent compliance during the follow-up period. In each group 20 children (40 per cent) required a blood transfusion. In the remaining 60 children, after 2 weeks the haemoglobin had risen 3.7 g/dl in the ferrous-supplemented group compared to 3.5 g/dl in the non-ferrous group. Thereafter, the increase in haemoglobin in both groups was steady. At follow-up measurements, the groups did not differ for haemoglobin levels. The mean haemoglobin at 12 weeks was 9.2 and 9.0 g/dl, respectively. It was concluded that iron supplementation did not have any effect on the rate of parasitaemia and on parasite density during the 12 weeks. However, the iron-supplemented group had a significantly increased morbidity from other causes than malaria. It appears that iron does not have an effect on the recovery of haemoglobin level in children with malaria-associated anaemia. This study provides no evidence supporting routine iron supplementation to these children.


Optical triode operation characteristics of nonlinear étalons.
Optical triode operation characteristics of nonlinear étalons such as on-off ratio, fan-out, thresholding power, and switching time are strongly dependent on material, cavity parameters, operating conditions (detuning and operating power), and operating method. We studied these dependences and trade offs with regard to various factors, especially operating conditions. Applying the results, optical gate operations of both transmission-and reflection-type devices were demonstrated.


Influence of iron status in the response to the deferoxamine test.
The study presented here was carried out to evaluate the possible relationship between serum iron and iron transferrin saturation with the response to the deferoxamine test in 86 chronic renal failure patients undergoing hemodialysis. The deferoxamine test was performed as a diagnostic tool for aluminum intoxication. Basal serum aluminum levels correlated with: (1) serum aluminum levels after the infusion of deferoxamine (r = 0.45; P < 0.05); (2) serum iron levels (r = -0.26; P < 0.05), and; (3) iron transferrin saturation (r = -0.33; P < 0.05). The increase in serum aluminum levels after deferoxamine administration (DAI) showed a negative relationship with serum iron levels (r = -0.23; P < 0.05) and iron transferrin saturation (r = -0.26; P < 0.05). The correlations improved when analysis of this study included only those patients with high serum iron levels or high iron transferrin saturation (r = -0.55). Patients with low probability of having aluminum overload (serum iron levels < 40 micrograms/L and DAI < 150 micrograms/L) had significantly higher values of serum iron, iron transferrin saturation, and serum ferritin levels compared with those patients with a high probability of having aluminum overload (serum aluminum levels > 40 micrograms/L and DAI > 150 micrograms/L). The study presented here suggests that patients who have indicators of iron repletion would tend to have lower increases in serum aluminum levels after the challenge with deferoxamine and presumably a higher incidence of false negative results with the deferoxamine test. These findings indicate that iron measurements must be always taken into account when interpreting the deferoxamine test.


Combining PPI with qualitative research to engage 'harder-to-reach' populations: service user groups as co-applicants on a platform study for a trial.
It is recommended that research studies are carried out with or by patients and the public through their involvement from the beginning and in as many stages as possible (known as PPI). Some studies formally invite patients and the public to participate in interviews and focused group discussions to collect views about topics (known as qualitative research). In our study on financial incentives for giving up smoking in pregnancy and breastfeeding, we combined both PPI and qualitative research to include the views of women with a range of experiences of smoking and breastfeeding. We involved two mother and baby groups in disadvantaged areas of North East Scotland and North West England as research partners on our team. First, we asked members to comment on our research plans and documents, which is standard PPI. Second, we asked members to participate in voice recorded discussions, contributing to qualitative research data. These discussions revealed different views from those that we heard through research interviews. They allowed us to develop more relevant research tools and resources. Members also helped us to identify people outside the groups who we could interview. Combining involvement and participation helped us to include the views of a wide range of women from 'harder-to-reach' groups who don't usually take part in research. This was important because the research was intended for women who could benefit from incentives to stop smoking in pregnancy and breastfeed, often present in such groups. Positive continuing relationships and trust improved on involvement or participation alone. . Patient and public involvement (PPI) in all research studies is recommended from the earliest point and in as many stages as possible. Qualitative research is also recommended in the early stages of designing complex intervention trials. Combining both together might enable inclusion of 'harder-to-reach' perspectives from the target population(s), particularly when the research is intended for their benefit. However, the interface between PPI and qualitative research has received little attention. In a multi-disciplinary, mixed methods study to inform the design of incentive trials for smoking cessation in pregnancy and breastfeeding, we combined PPI and qualitative research, with some overlap. Mother and baby groups from two geographically separate disadvantaged areas, with diverse experiences of the smoking and breastfeeding, but no training or previous involvement in research, were recruited as PPI research grant co-applicants. An iterative partnership approach facilitated involvement in research conduct and design across all project phases. Group PPI members were also invited to contribute to more formal qualitative data collection, as and when indicated by the research questions, and emerging analysis. We engaged with 'harder-to-reach' women in mother and baby group settings, rather than in academic or home environments. These settings were relaxed and informal, which facilitated rapport-building, disclosures of unexpected information and maintained trust. Twenty-one women participated in standard PPI activities: feedback on study protocols and documents; piloting questionnaires and interview schedules. PPI members voiced some different perspectives from those captured within the qualitative dataset. Nineteen participated in focused qualitative research. Novel aspects were audio recorded PPI discussions, which contributed qualitative data; first, to interpret systematic review findings and construct intervention vignettes for use in the qualitative research; second, to assist with recruitment to improve sample diversity in the formal qualitative dataset; and third, to translate theory and findings presented in a researcher generated logic model into a lay tool. This had face validity for potential trial participants and used the metaphor of a ladder. Combining and overlapping PPI and qualitative research added 'harder-to-reach' contributions, sample diversity, trust and engagement in creative approaches beyond what could be achieved through PPI or qualitative research alone.


The tissue-specific transcription factor Pit-1/GHF-1 binds to the c-fos serum response element and activates c-fos transcription.
Pit-1, a POU domain-containing transcription factor, is involved in two functions in the pituitary: PRL and GH tissue-specific expression and somatolactotroph cells expansion. To analyze the molecular basis of the latter function, we tested whether Pit-1 can directly transactivate expression of an early marker of cell cycle initiation, the c-fos gene. We show that Pit-1 overexpression in PC12 cells, which do not express Pit-1, increases c-fos expression. Moreover, cAMP-induced c-fos promoter activity is decreased in the somatolactotroph cell line GH3 when Pit-1 expression is reduced by hybrid arrest with an antisense sequence complementary to Pit-1 cDNA. In contrast to hormonal genes regulation, where it has been shown that any Pit-1 phosphorylation site is involved, we show that the Pit-1 phosphorylation sites are required to allow increase of c-fos promoter activity by Pit-1. We further show, by gel shift analyses, that Pit-1 is able to specifically bind the serum response element sequence present within the c-fos promoter but with a lesser affinity than the Pit-1 response element. Taken together, these results demonstrate that the tissue-specific transcription factor Pit-1 is able to enhance expression of genes involved in cell cycle initiation, suggesting that this mechanism allows Pit-1 to increase somato-lactotroph cell proliferation.


Prader-Willi Syndrome: Genetics and Behavior.
Since its inception, the John F. Kennedy Center has attempted to overcome developmental problems, which create restrictive barriers to the participation of individuals with specific disabilities in our broader society. Some of Nicholas Hobbs's earliest efforts involved developing strategies for preventing children's emotional and behavior problems, which interfered with their later full participation in society. Other investigators in the Kennedy Center explored ways of reducing dysfunctional repetitive movement problems and self-injury commonly associated with autism and severe mental retardation. We have become concerned about a group of people who have the potential to live largely independently (or semi-independently), to work at meaningful jobs in the community, and to make full use of the same recreational and leisure opportunities as other members of society but who are prevented from doing so because of a life-threatening behavior problem. Prader-Willi syndrome (PWS) is a genetic developmental disability characterized by a group of specific behavioral features of which an insatiable appetite is the most striking. PWS is the most commonly known genetic cause of obesity. The eating disorder associated with PWS can be so severe as to be life threatening, including eating to the point of stomach rupture and death. Though a cluster of commonly covarying clinical features are exhibited by people with this syndrome, only the eating disorder is common to all affected individuals. PWS shares behavioral features with other disorders and disabilities, such as obsessive compulsive disorder and autism, but only PWS includes the unique combination of characteristics that distinguish this syndrome. Because eating disorders such as bulimia and anorexia nervosa also share features with PWS, any light that could be shed on the causes and treatment of the eating disorder in PWS could potentially have far-reaching implications for other eating disorders as well. In this article, we review the behavioral, cognitive, and other psychological features of PWS and explore their relationships to known genetic mechanisms.


Autotransfusion in aortic surgery: the Haemocell System 350 cell saver.
Autotransfusion was performed during elective abdominal aortic reconstruction in ten patients using the recently developed Haemocell System 350. A mean of 60 per cent of total blood loss was salvaged, and during operation each patient was autotransfused 1 unit. Good preservation of cellular components, including platelets, was seen after processing with the device, which uses a vortex mixing filter for cell separation. There was no evidence of coagulopathy; mean free plasma haemoglobin levels were slightly raised (17 mg/dl) and plasma heparin concentration was negligible (0.10 units/ml) 4 h after surgery. A transient drop in plasma fibrinogen levels and the appearance of fibrin degradation products in low concentrations (mean 1.5 mg/l) were seen. Oxyhaemoglobin dissociation curves showed the salvaged red blood cells to have a normal affinity for oxygen. Renal and hepatic function remained unaltered and there were no complications attributable to autotransfusion. The device was easy to handle and a trained operator was not required.


Point of diminishing returns: when does gestational weight gain cease benefiting birthweight and begin adding to maternal obesity?
This study is a reanalysis of the first scientific paper published by one of the authors, originally coauthored with Dr. Roy H. Petrie. In honor of Dr. Petrie, these data have been reanalyzed to re-evaluate the data using more sophisticated techniques and to expand on the original findings. This reanalysis examines the contribution of maternal weight gain to infant birthweight and retained maternal weight in the immediate postpartum period, and the effect of weight gains below, at, and above the Institute of Medicine (IOM) guidelines on both infant birthweight and retained maternal weight in the postpartum period. The study population included 487 term, uncomplicated, singleton pregnancies. Body mass index (BMI) was calculated for each woman, and categorized as underweight, normal weight, or overweight. Maternal retained weight was calculated as postpartum weight 2 days after delivery minus pregravid weight. Every kilogram of gestational weight gain increased birthweight by 44.9 g for underweight women, 22.9 g for normal weight women, and 11.9 g for overweight women. For every kilogram of retained weight, birthweight was increased by 35.6 g for underweight women, 15.9 g for normal-weight women, and 5.1 g for overweight women. Increasing weight gains from below to equal to IOM guidelines increased birthweight and maternal retained weight by 317 g (11%) (P < 0.01) and 5 kg (P < 0.01), respectively, for underweight women; 141 g (4.4%) (P < 0.02) and 6.2 kg (P < 0.01), respectively, for normal-weight women; and 200 g (6.4%) (NS) and 6.4 kg (P < 0.01), respectively, for overweight women. Increasing weight gains from equal to above the IOM guidelines increased birthweight and maternal retained weight by an additional 299 g (9.4%) (P < 0.02) and 7.3 kg (P < 0.01), respectively, for underweight women; an additional 196 g (5.9%) (P < 0.01) and 5.9 kg (P < 0.01), respectively, for normal weight women; and an additional 9 g (0.3%) (NS) and 8.3 kg (P < 0.01), respectively, for overweight women. These findings suggest that, beyond a certain level of weight gain, there is a point of diminishing returns (increase in birthweight) at the expense of increasing maternal postpartum obesity for the woman who has gained excessively.


Familial neonatal atrial tachycardia.
A father and his two sons each presented with atrial tachycardia in the newborn period. The father went on to develop dilated cardiomyopathy. The first son (who also had transposition of the great arteries) died from the arrhythmia after surgery. The second son is currently successfully managed pharmacologically.


Improvement and sustainability of walking ability with hybrid assistive limb training in a patient with cerebral palsy after puberty: a case report.
[Purpose] Cerebral palsy is one of the most common causes of childhood physical disability affecting motor development. Gait training with a wearable-robot, such as the Hybrid Assistive Limb, has been reported to improve gait ability in patients with chronic motor disabilities; however, there are no reports concerning the sustained improvement of walking ability with its use in patients with cerebral palsy. We present our observations for the use of Hybrid Assistive Limb gait training in a postpubescent cerebral palsy patient. [Participant and Methods] A 17-year-old male with spastic cerebral palsy could only ambulate slightly using a crouch gait posture and with the aid of a walker. Hybrid Assistive Limb training was performed thrice weekly for 4 weeks (total of 12 sessions) along with concurrent daily physical therapy. The follow-up period was 7 months after the intervention. [Results] The intervention resulted in improvements in the patient's gait speed, proportion of the stance phase in a gait cycle, step length, and the flexion angle of the knees at initial contact and during late stance phase, which was sustained for 7 months following the intervention. [Conclusion] Our observations suggest that Hybrid Assistive Limb training may effectively improve and sustain walking ability even among postpubescent cerebral palsy patients who have a decreased walking ability.


Di-Tyrosine Crosslinking and NOX4 Expression as Oxidative Pathological Markers in the Lungs of Patients with Idiopathic Pulmonary Fibrosis.
Idiopathic pulmonary fibrosis (IPF) is a noninflammatory progressive lung disease. Oxidative damage is a hallmark of IPF, but the sources and consequences of oxidant generation in the lungs are unclear. In this study, we addressed the link between the H2O2-generating enzyme NADPH oxidase 4 (NOX4) and di-tyrosine (DT), an oxidative post-translational modification in IPF lungs. We performed immunohistochemical staining for DT and NOX4 in pulmonary tissue from patients with IPF and controls using validated antibodies. In the healthy lung, DT showed little or no staining and NOX4 was mostly present in normal vascular endothelium. On the other hand, both markers were detected in several cell types in the IPF patients, including vascular smooth muscle cells and epithelium (bronchial cells and epithelial cells type II). The link between NOX4 and DT was addressed in human fibroblasts deficient for NOX4 activity (mutation in the CYBA gene). Induction of NOX4 by Transforming growth factor beta 1 (TGFβ1) in fibroblasts led to moderate DT staining after the addition of a heme-containing peroxidase in control cells but not in the fibroblasts deficient for NOX4 activity. Our data indicate that DT is a histological marker of IPF and that NOX4 can generate a sufficient amount of H2O2 for DT formation in vitro.


[Analysis of diphtheria antibody levels in healthy population in Beijing municipal, 2007].
To investigate the diphtheria antibody level in healthy population in Beijing. 10 age groups (< 1, 1 to 4, 5 to 9, 10 to 14, 15 to 19, 20 to 24, 25 to 29, 30 to 34, 35 to 39, and > or =40) were sampled by the Multi-stage stratified sampling method in 9 districts in Beijing, and 2 003 sera from healthy population were collected. The diphtheria antibody was determined with ELISA method. The diphtheria antibody-positive rate was 60.26%, and the antibody concentration was 0.62 IU/ml. A trend of decreasing in the antibody concentration was observed with increasing age and years after immunization. Antibody levels were the lowest in healthy people between 25-40 years old. It was predicted that a large scale of diphtheria outbreak would not occur recently in Beijing. It is recommended that for all adults diphtheria toxoids booster immunization should be conducted every 10 years for all adults.


Short report: Dynamics of Plasmodium falciparum malaria after sub-optimal therapy in Uganda.
We followed parasite genotypes of 75 patients for 42 days after treatment of uncomplicated malaria with chloroquine + sulfadoxine-pyrimethamine in Kampala, Uganda. Infections were complex (mean, 2.88 strains) and followed three patterns: 27% of patients eliminated all strains and remained parasite-free, 48% had a long aparasitemic interval followed by reappearance of original strains after 3-33 days (mean, 9.2 days), and 25% failed to clear original strains and required therapy after 3-35 days (mean, 17 days). These results highlight the complexity of malaria in Africa and have implications for efficacy trials, because missing late reappearances of strains could lead to misclassification of outcomes.


Characterization of equine oviductal proteins synthesized and released at estrus and at day 4 after ovulation in bred and nonbred mares.
Proteins synthesized and released in vitro by oviducts collected from horse mares during estrus and at day 4 after ovulation for bred and nonbred mares were examined by two-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis (2-D SDS PAGE) and fluorography. Ampullary and isthmic regions both produced a wide array of nondialyzable proteins in culture. Major proteins or groups of proteins identified according to relative molecular weight (kDa) and apparent isoelectric point (pI) were at 100 kDa, pI 8; 100-200 kDa, pI 6; 150 kDa, pI 4.5; 60-100 kDa, pI 4; and an array of polypeptides at 21-22 kDa, pI 5-6. Oviductal secretory activity, measured by incorporation of radiolabeled amino acids into nondialyzable macromolecules released into incubation medium, was greater (P < .01) for the ampullary than the isthmic oviductal region. No consistent differences were observed in fluorograms between estrus vs. day 4 after ovulation, ampulla vs. isthmus, ipsilateral vs. contralateral to the corpus luteum or largest follicle, oviducts from bred vs. nonbred mares, or mare ages. Dialyzed medium from ampullary and isthmic regions of oviducts was subjected to 1-D or 2-D SDS PAGE followed by western blotting utilizing an antiserum directed against human retinol binding protein (RBP). The family of 21-22 kDA polypeptides was identified as immunoreactive RBP.


The effects of rigid motions on elastic network model force constants.
Elastic network models provide an efficient way to quickly calculate protein global dynamics from experimentally determined structures. The model's single parameter, its force constant, determines the physical extent of equilibrium fluctuations. The values of force constants can be calculated by fitting to experimental data, but the results depend on the type of experimental data used. Here, we investigate the differences between calculated values of force constants and data from NMR and X-ray structures. We find that X-ray B factors carry the signature of rigid-body motions, to the extent that B factors can be almost entirely accounted for by rigid motions alone. When fitting to more refined anisotropic temperature factors, the contributions of rigid motions are significantly reduced, indicating that the large contribution of rigid motions to B factors is a result of over-fitting. No correlation is found between force constants fit to NMR data and those fit to X-ray data, possibly due to the inability of NMR data to accurately capture protein dynamics.


Fatality in a wine vat.
Intoxication with carbon dioxide (CO2), a nonexplosive, colorless, and odorless gas does not cause any clinical symptoms or signs, with the occasional exception of sudation. Carbon dioxide is principally used in the food industry (70% of CO2 production), in particular to preserve foods and to carbonate beverages. Most fatalities resulting from CO2 intoxication are accidental and occur either in closed spaces or when dry ice is used in the food industry. In this case report, a 42-year-old male winemaker engineer was found dead, his head inside a wine vat that had been filled with grapes on the previous day and supplemented with dry ice to improve the taste of wine.


Lipophilic impurity of phenol red is a potent cation transport modulator.
Previously, we described substantial alterations in the Na+ and K+ homeostasis of human skin fibroblasts following removal of fetal bovine serum (FBS). Herein, we report that FBS removal per se does not cause any cellular ionic changes unless a lipophilic impurity of commercial phenol red preparations is present. This substance accelerates 86Rb+ efflux four to seven times, causes a four to eight time increase in cellular Na+, and a 40-70% reduction in cellular K+ contents. FBS (10%) or albumin (0.8%) appears to bind the impurity thus inhibiting its action. The increased cellular Na+ and decreased K+ contents do not return to baseline within 4 hours following the removal of the phenol red extract. However, albumin completely reverses the cellular cationic changes that develop during a 2 hour exposure of the cells to the free substance. The reversibility of its action by albumin suggests that the substance exerts its effect on or within the cell membrane and not intracellularly. Among seven different cell lines tested the 86Rb+ efflux from, and the Na(+)-K+ contents of, COS-7 and Hs68 cells also responded to unpurified phenol red in a way similar to human fibroblasts. The amount of the phenol red contaminant is manufacturer dependent. As little as 0.5 microM phenol red, from one vendor, was sufficient to elicit response in the 86Rb+ efflux. Given that the impurity is unlikely to be more than a small fraction of phenol red, it seems to be a potent ionic transport modulator. Based on these results, the presence of commercial phenol red in serum-free growth or test media, including the increasing variety of chemically defined culture media, should be considered as a potential confounding factor in measurements that depend on intracellular Na(+)-K+ homeostasis. The findings of such earlier studies may need to be reconsidered if the cells were exposed to unbound phenol red. We recommend that, until the manufacturers further refine their product, phenol red be purified by ether extraction before its use. The evaluation of the potential physiologic or pharmacologic relevance of this potent cation transport modulator awaits its isolation.


9-cis-retinoic acid regulates the expression of the muscle determination gene Myf5.
Myf5 is a member of the MyoD family, a set of four helix-loop-helix transcription factors that controls myogenic differentiation. The Myf5 gene has both in vivo and in vitro expression patterns consistent with an involvement in the first events of myogenesis, such as acquisition and/or maintenance of myogenic "determined" phenotype. To date, very little is known about the mechanism underlying the tight regulation of Myf5 expression. We report here that retinoic acid (RA) reduces the level of Myf5 message in both mouse C2 and rat L6 cell lines, probably at the transcriptional level, because Myf5 mRNA stability is not affected by RA. This repression is dose dependent, starting at 0.1 microM of all-trans RA, and is not abrogated by cycloheximide, suggesting a direct involvement of RA receptors in the control of Myf5 expression. Furthermore, we compared the efficiency of natural (all-trans RA and 9-cis RA) or synthetic (TTNPB) retinoids that differentially activate the two families of RA receptors, RA receptors and retinoid X-receptors (9-cis RA). As 9-cis RA is about 10 times more efficient than all-trans RA in repressing Myf5, whereas TTNPB, which preferentially activates RA receptors, is far less potent, our data provide evidence for an important role of ligand-bound retinoid X-receptors in the mediation of this inhibition.


Process, quality and challenges of diabetes care in primary care: a study of district health network in Thailand.
This study aimed to describe the process of care, assess the quality of care based on defined indicators, and identify challenges associated with providing diabetes care via sub-district health promotion hospital (SHPH) facilities in Thailand. Primary care policy has directed that diabetes care be delivered via SHPH in order to reduce hospital congestion and minimize travel costs for patients. Limited data is available regarding the structure for providing care. Likewise, barriers to delivery of optimal care have not been well defined, especially from the perspective of health care providers. This study employed mixed-methods research, which included semi-structured interviews to gain insights into the current diabetes care process, a descriptive study to evaluate quality of care, and use of a focus group to identify challenges associated with delivery of diabetic care via SHPH. Diabetes care processes in primary care included multiple steps and involved collaboration between various health care providers at both the hospital and SHPH. Four process indicators and one outcome had been achieved but performance of other indicators was apparently low. Three factors were found to pose challenges to providing this service: the resources of the health service, the delivery of services, and patient factors. SHPH require additional support, particularly in the areas of primary care workforce, finance, medical device procurement, and patient information systems. While delivery of diabetes care via primary care centers has been well established in Thailand, regional differences in the quality of care persist. Additional support is required to strengthen the primary care system nationwide.


[TSH receptor antibody in hyperthyroid patients due to Graves' disease treated with antithyroid drugs].
As an immunologic process, TSH receptor antibody (TRab) may be synthesized by the lymphocytes within the thyroid gland. Two techniques were devised to express this TRap activity: a) thyroid stimulating immunoglobulin (TSI) expressed as thyroid c AMP synthesis and b) TSH binding inhibiting immunoglobulin (TBII) expressed as TSH displacement. In general, serum TSI and TBII activity correlated well with each other in hyperthyroid patients. Measurement of TSI and TBII is useful to assess improvement of immunologic abnormality induced by antithyroid drugs. The data so far gathered indicated that TRab disappears from the blood in about 70-80% of hyperthyroid patients in response to antithyroid drugs. However, this does not indicate that intrathyroidal TRab synthesis has ceased, since thyroglobulin is still secreted supernormally and T3 fails to suppress the thyroid in some patients. On the other hand, normalization of thyroglobulin and absence of TRab in the blood indicated complete normalization in the patients as evidenced by positive T3 suppressibility. By using a number of new drugs, further efforts must be made to completely normalize immunologic abnormality in 100% of patients. Recurrence of hyperthyroidism of Graves' disease is generally associated with re-appearance of TRab in the blood in most of the recurrent patients after discontinuation of antithyroid drugs.


Corneoconjunctival manifestations of lymphoma in three dogs.
An 8-year-old Shih Tzu, a 5-year-old Maltese, and a 10-year-old Maltese presented with conjunctival hyperemia and peripheral corneal edema. Severe conjunctival thickening with varying degrees of corneal extension was observed. Cytological examination showed many large lymphocytes with malignant changes in the conjunctiva which was consistent with findings in fine-needle aspiration samples taken from regional lymph nodes. They were diagnosed as having Stage V multicentric lymphoma. When conjunctival thickening is observed in canine patients with multicentric lymphoma, conjunctival metastasis with infiltration of neoplastic lymphoid cells should be included in the differential diagnosis.


[Computer-tomographic anatomy of the posterior cranial fossa].
Bony basis of the posterior cranial fossa (PCF) was studied on the spiral computer tomograms of 160 patients of both genders without skull bone and brain pathology. Fundamental PCF radiometric parameters (length, width, depth) were determined. According the variants of combination of extreme values of these parameters, 5 most common forms of PCF were distinguished (long narrow deep, long broad shallow, long narrow shallow, long broad deep, short narrow shallow); their linear and angular radiometric characteristic was presented. Radiometric parameters which are significant for the individual planning of operative approaches to CFP structures, were noted.


Patients with cancer referred to hospice versus a bridge program: patient characteristics, needs for care, and survival.
The purpose of this study was to compare the characteristics and needs of patients with advanced cancer who were referred to hospice with those referred to a prehospice "bridge" program that is staffed by hospice nurses. Data were gathered through retrospective review of computerized clinical records using precoded data fields of 284 patients with cancer enrolled in a bridge program and 1,000 who enrolled in a hospice program. Patient characteristics, needs for supportive care at the time of enrollment, and survival were assessed. Bridge patients were less likely to have Medicare or Medicaid (43% v 72%; odds ratio, 0.30; P <.001) and were younger (69 v 73 years, rank sum test; P <.001), more likely to be married (59% v 43%; odds ratio, 1.90; P <.001), and more likely to be in the highest income category (14% v 10%; odds ratio, 1.77; P =.009). Bridge patients had at least as many needs for care as did patients in hospice. Bridge patients lived significantly longer (median, 46 v 19 days; log-rank test of survivor functions, P <.001). Patients referred to this bridge program had prognoses that are significantly better than those of patients who enter hospice, but they have needs for supportive care that are at least as great. These findings underscore the importance of initiatives to extend some of the benefits of hospice care to a wider population of patients and should encourage the analysis of similar programs' ability to meet these needs.


Florid cemento-osseous dysplasia: A rare case report evaluated with cone-beam computed tomography.
A 29-year-old systemically healthy female patient presented to our department. Cone-beam computed tomographic images showed multiple well-defined sclerotic masses with radiolucent border in both right and left molar regions of the mandible. These sclerotic masses were surrounded by a thin radiolucent border. We diagnosed the present pathology as florid cemento-osseous dysplasia and decided to follow the patient without taking biopsy. For the patient, who did not have any clinical complaints, radiographic followupis recommended twice a year. The responsibility of the dentist is to ensure the follow-up of the diagnosed patients and take necessary measures for preventing the infections.


Profiling Humoral Immune Responses to Clostridium difficile-Specific Antigens by Protein Microarray Analysis.
Clostridium difficile is an anaerobic, Gram-positive, and spore-forming bacterium that is the leading worldwide infective cause of hospital-acquired and antibiotic-associated diarrhea. Several studies have reported associations between humoral immunity and the clinical course of C. difficile infection (CDI). Host humoral immune responses are determined using conventional enzyme-linked immunosorbent assay (ELISA) techniques. Herein, we report the first use of a novel protein microarray assay to determine systemic IgG antibody responses against a panel of highly purified C. difficile-specific antigens, including native toxins A and B (TcdA and TcdB, respectively), recombinant fragments of toxins A and B (TxA4 and TxB4, respectively), ribotype-specific surface layer proteins (SLPs; 001, 002, 027), and control proteins (tetanus toxoid and Candida albicans). Microarrays were probed with sera from a total of 327 individuals with CDI, cystic fibrosis without diarrhea, and healthy controls. For all antigens, precision profiles demonstrated <10% coefficient of variation (CV). Significant correlation was observed between microarray and ELISA in the quantification of antitoxin A and antitoxin B IgG. These results indicate that microarray is a suitable assay for defining humoral immune responses to C. difficile protein antigens and may have potential advantages in throughput, convenience, and cost.


Comparative study of the binding characteristics to and inhibitory potencies towards PARP and in vivo antidiabetogenic potencies of taurine, 3-aminobenzamide and nicotinamide.
Poly(ADP-ribose) is a NAD+-requiring, DNA-repairing, enzyme playing a central role in pancreatic beta-cell death and in the development of endothelial dysfunction in humans and experimental animals. PARP activation is also relevant to the development of complications of diabetes. Hence, agents capable of inhibiting PARP may be useful in preventing the development of diabetes and in slowing down complications of diabetes. PARP inhibition was assessed with a colorimetric assay kit. Molecular docking studies on the active site of PARP were conducted using the crystalline structure of the enzyme available as Protein Data Bank Identification No. 1UK1. Type 2 diabetes was induced in male Sprague-Dawley rats with streptozotocin (STZ, 60 mg/kg, i.p.). The test compounds (3-aminobenzamide = 3-AB, nicotinamide = NIC, taurine = TAU) were given by the i.p. route 45 min before STZ at 2.4 mM/kg (all three compounds) or 1.2 and 3.6 mM/kg (only NIC and TAU). Blood samples were collected at 24 hr after STZ and processed for their plasma. The plasma samples were used to measure glucose, insulin, cholesterol, triglycerides, malondialdehyde, nitric oxide, and glutathione levels using reported methods. 3-AB, NIC and TAU were able to inhibit PARP, with the inhibitory potency order being 3-AB>NIC> or =TAU. Molecular docking studies at the active site of PARP showed 3-AB and NIC to interact with the binding site for the nicotinamide moiety of NAD+ and TAU to interact with the binding site for the adenine moiety of NAD+. While STZ-induced diabetes elevated all the experimental parameters examined and lowered the insulin output, a pretreatment with 3-AB, NIC or TAU reversed these trends to a significant extent. At a dose of 2.4 mm/kg, the protective effect decreased in the approximate order 3-AB>NIC> or =TAU. The attenuating actions of both NIC and TAU were dose-related except for the plasma lipids since NIC was without a significant effect at all doses tested. At equal molar doses, 3-AB was generally more potent than either TAU or NIC as an antidiabetogenic agent, but the differences were not as dramatic as would have been predicted from their differences in PARP inhibitory potencies. NIC and TAU demonstrated dose-related effects, which in the case of TAU were only evident at doses > or =2.4 mM/kg. The present results also suggest that in the case of NIC and TAU an increase in dose will enhance the magnitude of their attenuating actions on diabetes-related biochemical alterations to that achieved with a stronger PARP inhibitor such as 3-AB. Hence, dosing will play a critical role in clinical studies assessing the merits of NIC and TAU as diabetes-preventing agents.


Novel approximation of misalignment fading modeled by Beckmann distribution on free-space optical links.
A novel accurate and useful approximation of the well-known Beckmann distribution is presented here, which is used to model generalized pointing errors in the context of free-space optical (FSO) communication systems. We derive an approximate closed-form probability density function (PDF) for the composite gamma-gamma (GG) atmospheric turbulence with the pointing error model using the proposed approximation of the Beckmann distribution, which is valid for most practical terrestrial FSO links. This approximation takes into account the effect of the beam width, different jitters for the elevation and the horizontal displacement and the simultaneous effect of nonzero boresight errors for each axis at the receiver plane. Additionally, the proposed approximation allows us to delimit two different FSO scenarios. The first of them is when atmospheric turbulence is the dominant effect in relation to generalized pointing errors, and the second one when generalized pointing error is the dominant effect in relation to atmospheric turbulence. The second FSO scenario has not been studied in-depth by the research community. Moreover, the accuracy of the method is measured both visually and quantitatively using curve-fitting metrics. Simulation results are further included to confirm the analytical results.


Foodborne Illness Associated with a Pig Roast.
Roasting of whole pigs for summer picnics is popular, but technically difficult. We report an outbreak of gastroenteritis which followed a pig roast in Colorado. Twenty (35%) of 57 guests who had attended the roast had nausea, diarrhea, abdominal cramps, vomiting, or fever. An investigation implicated pork as the vehicle of transmission (p = 0.003, Fisher exact test). The 11 stool specimens tested were not cultured anaerobically, but the illness was strongly suggestive of Clostridium perfringens gastroenteritis. An environmental investigation revealed deficiencies in both storage and cooking of the commercially prepared pig. To prevent foodborne outbreaks of illness resulting from whole pig roasts, suppliers should caution customers about adequate cooking processes, customers should be aware of refrigeration requirements if the animal is to be stored before cooking, meat thermometers should be used to monitor internal cooking temperatures, other food should not be cooked inside the pig carcass during roasting, and leftover meat should be promptly cooled for later consumption.


Percutaneous stent implantation into coronary arteries in infants.
To investigate the feasibility, procedural techniques, safety, and overall potential of percutaneous coronary angioplasty and stent implantation in infants with coronary artery disease and acute coronary syndrome. Despite extensive experience in adult patients, percutaneous coronary intervention remains uncommon in children and extremely rare in infants. Retrospective review including all children who underwent percutaneous coronary angioplasty in Rady Children's Hospital-San Diego during a period of 4 years. Seven children including four children less than 15 months of age underwent percutaneous coronary intervention with coronary stent implantation in the proximal portion of the left or right coronary arteries. Successful stent placement with excellent revascularization was achieved in all cases. Mean coronary artery diameter was 0.65 mm prior to stent placement. Balloon angioplasty resulted in suboptimal resolution of coronary stenosis, thus bare metal stents were implanted in all cases, dilated to a mean of 2.5-mm internal diameter. Average intervention-free period was 434 days after stent implantation. In-stent re-stenosis and stent thrombosis did not occur if the implanted stent diameter was greater than 2.5 mm and the patient received dual anti-platelet therapy. Our experience suggests that coronary artery stent implantation is a feasible and relatively safe palliative option in infants and toddlers with coronary stenosis. It is a viable strategy for bridging patients with acute ischemia or poor ventricular function to elective surgical revascularization or transplantation.


Identification of Thiols in Yellow Onion (Allium cepa L.) Using Solvent Vented Large Volume Injection GC-MS.
Thiols are often highly odor active molecules and as such can significantly contribute to aroma while being present at extremely low concentrations. This paper details the identification of thiols in yellow onion juice by solvent extraction followed by thiol enrichment using a mercuric agarose gel column. Due to the inherent thermal instability and low concentrations of thiols in onion, chromatographic analysis utilized larger volume solvent elimination injections. New sulfur compounds in onion included 1,1-propanedithiol, bis-(1-sulfanylpropyl)-sulfide, 1-methylsulfanyl-1-propanethiol, 1-propylsulfanyl-1-propanethiol, and 1-allylsulfanyl-1-propanethiol. A discussion on the potential route of formation for each compound is included along with the orthonasal and retronasal evaluations of the synthesized molecules. This work investigated and identified 5 newly identified compounds present in onions that can impart onion character at low concentrations levels.


Chlorine residuals and haloacetic acid reduction in rapid sand filtration.
It is quite rare to find biodegradation in rapid sand filtration for drinking water treatment. This might be due to frequent backwashes and low substrate levels. High chlorine concentrations may inhibit biofilm development, especially for plants with pre-chlorination. However, in tropical or subtropical regions, bioactivity on the sand surface may be quite significant due to high biofilm development--a result of year-round high temperature. The objective of this study is to explore the correlation between biodegradation and chlorine concentration in rapid sand filters, especially for the water treatment plants that practise pre-chlorination. In this study, haloacetic acid (HAA) biodegradation was found in conventional rapid sand filters practising pre-chlorination. Laboratory column studies and field investigations were conducted to explore the association between the biodegradation of HAAs and chlorine concentrations. The results showed that chlorine residual was an important factor that alters bioactivity development. A model based on filter influent and effluent chlorine was developed for determining threshold chlorine for biodegradation. From the model, a temperature independent chlorine concentration threshold (Cl(threshold)) for biodegradation was estimated at 0.46-0.5mgL(-1). The results imply that conventional filters with adequate control could be conducive to bioactivity, resulting in lower HAA concentrations. Optimizing biodegradable disinfection by-product removal in conventional rapid sand filter could be achieved with minor variation and a lower-than-Cl(threshold) influent chlorine concentration. Bacteria isolation was also carried out, successfully identifying several HAA degraders. These degraders are very commonly seen in drinking water systems and can be speculated as the main contributor of HAA loss.


Iodine nutrition and the risk from radioactive iodine: a workshop report in the chernobyl long-term follow-up study.
The major fallout of radionuclides from the nuclear power station accident at Chernobyl on 26 April, 1986, occurred in regions of Ukraine and Belarus that are believed to be moderately deficient in dietary iodine. On 17 November, 2000, in conjunction with the Ukraine-Belarus-USA study of developing thyroid disease in a cohort of individuals exposed as children, a workshop was held to review what is known about iodine nutrition in the region, how this might influence the risk of thyroid tumor formation from radioiodine, and whether and how iodine nutrition should be monitored in this long-term project. This report is a summary of the workshop proceedings. Although no precise information about iodine intake in 1986 was found, the prevalence of mild goiter in the region's children suggested iodine deficiency and urinary iodine measurements begun in 1990 indicated that mild to moderate deficiency existed. Increased thyroid iodine uptake and increased thyroid size in 1986 resulting from iodine deficiency would have had counteracting influence on the thyroid radiation dose and knowledge of these parameters is required for dose reconstruction. More problematic is the possible role of iodine deficiency in the years following the accident. Theoretically, the resulting increase in thyroid cellular activity might increase the risk of tumorigenesis but experimental or clinical evidence supporting this hypothesis is meager or absent. Despite this limitation it was considered important to monitor iodine nutrition in the cohort subjects in relation to their place of residence and over time. Methods to accomplish this were discussed.


Annual report of the Australian National Enterovirus Reference Laboratory 2012.
In 2012 no cases of poliomyelitis were reported through clinical surveillance in Australia, and poliovirus was not detected through virological surveillance. Australia conducts surveillance for cases of acute flaccid paralysis (AFP) in children less than 15 years as the main mechanism to monitor its polio-free status in accordance with World Health Organization (WHO) recommendations. Cases of AFP in children are notified to the Australian Paediatric Surveillance Unit or the Paediatric Active Enhanced Disease Surveillance System. In 2012 Australia reported 1.2 non-polio AFP cases per 100,000 children, meeting the WHO performance criterion for a sensitive system for the fifth year in a row. However the faecal specimen collection rate from AFP cases was 29%, which was well below the WHO target of 80%. Virological surveillance for poliovirus consists of two components. Firstly, the Enterovirus Reference Laboratory Network of Australia (ERLNA) reports on the typing of enteroviruses detected in or isolated from clinical specimens. Secondly, environmental surveillance is conducted at sentinel sites. These surveillance systems are co-ordinated by the National Enterovirus Reference Laboratory (NERL).


Plasma membrane potential of the alga dunaliella, and its relation to osmoregulation.
A fluorescent dye sensitive to membrane potential was used to follow the plasma-membrane potential in the unicellular halo-tolerant alga Dunaliella salina. The signal observed during dissipation of the plasma membrane potential by the addition of excess K(+) and valinomycin, or a protonophore, was taken as a measure of the preexisting potential. A resting potential of -85 to -100 millivolts (negative inside) was calculated. Following a hypertonic shock, the plasma membrane was rapidly hyperpolarized. This hyperpolarization was transient, and the algae resumed their resting potential about 30 minutes after the shock. The resting plasma membrane potential was decreased by vanadate and is concluded to be generated mostly by the plasma membrane ATPase of Dunaliella. The transient hyperpolarization following a hypertonic shock indicates, therefore, a transient activation of the ATPase. This is further corroborated by a rapid transient decrease in the intracellular ATP following a hypertonic shock and its inhibition by vanadate. It is suggested that activation of the plasma membrane ATPase may be the trigger for osmoregulation in Dunaliella.


Cholecystolithotomy, a new approach to reduce recurrent gallstone ileus.
The incidence of gallstone ileus (GSI) is increasing. Current treatment options include enterolithotomy with or without cholecystectomy and repair of the biliodigestive fistula. Although most surgeons defer the management of the biliodigestive fistula to avoid the associated morbidity and mortality, this can lead to increased rate of recurrence of GSI by the remaining gallstones. More than 130 cases of recurrent GSI were reported in published works, and the incidence of recurrent GSI is reported to be between 5% and 20%. Some cases of second recurrent attacks have also been reported. Most cases were reported in elderly women with faceted stones during the first 2 months from the first episode of GSI. This article reviews the current treatment options for more than 4,300 reported cases of GSI. A treatment algorithm is recommended based on the severity of the inflammation around the gallbladder, including cholecystolithotomy as a third treatment approach that aims to reduce the risk of recurrent GSI.


The Educational Gradient in Intake of Energy and Macronutrients in the General Adult and Elderly Population: The Tromsø Study 2015-2016.
Worldwide, there are socioeconomic inequalities in health and diet. We studied the relationship between education and nutrient intake in 11,302 women and men aged 40-96 years who participated in the seventh survey of the population-based Tromsø Study (2015-2016), Norway (attendance 65%). Diet was assessed using a validated food-frequency questionnaire. We examined the association between education and intake of total energy and macronutrients by sex using linear and logistic regression models adjusted for age, body mass index, leisure time physical activity and smoking. The intake of macronutrients was compared with the Nordic Nutrition Recommendations 2012. There was a positive association between education and intake of fiber and alcohol, and a negative association between education and intake of total carbohydrates and added sugar in both women and men. Participants with long tertiary education had higher odds of being compliant with the recommended intake of fiber and protein and the maximum recommended level for added sugar and had lower odds of being compliant with the recommended intake of total carbohydrates and the maximum recommended level for alcohol, compared to participants with primary education. Overall, we found that participants with higher education were more compliant with the Nordic Nutrition Recommendations 2012.


Anti-microbial peptides for plaque control and beyond.
Anti-microbial peptides perform many functions in the oral cavity. They may provide protection against microbial pathogens, assist in oral biofilm control, and function as an important part of the innate immune system in response to local and systemic infection. Synthetic versions of these peptides may be useful to supplement natural anti-microbial peptides or as therapeutic agents.


Receptors mediating the contractile effect of serotonin (5-HT) in the isolated common bile duct of guinea-pig.
The contractile effect of 5-HT in the isolated common bile ducts of guinea-pigs was studied. 5-HT, administered non-cumulatively, evoked contractions which were concentration-dependent. Responses due to the low concentrations of 5-HT were antagonised significantly by ketanserin (10(-7) M and 10(-6) M) and methysergide (10(-6)M and 10(-5) M) whereas those induced by the higher concentrations of 5-HT remained unchanged. Atropine (3 x 10(-8) and 10(-7) M) and ICS 205-930 (10(-7) M and 10(-6) in contrast inhibited the contractions elicited by high concentrations of 5-HT without altering significantly the responses due to the lower ones. The results led us to conclude that 5-HT evoked contractions at low concentrations are predominantly mediated by 5-HT2 receptors whereas those at high concentrations are dependent on acetylcholine release via the stimulation of 5-HT3 receptors.


Your face says it all: closeness and perception of emotional expressions among females.
The purpose of the present investigation was to assess whether interpersonal closeness facilitates earlier emotion detection as the emotional expression unfolds. Female undergraduate participants were either paired with a close friend or an acquaintance (n = 92 pairs). Participants viewed morphed movies of their partner and a stranger gradually shifting from a neutral to either a sad, angry, or happy expression. As predicted, findings indicate a closeness advantage. Close friends detected the onset of their partners' angry and sad expressions earlier than acquaintances. Additionally, close friends were more accurate than acquaintances in identifying angry and sad expressions at the onset, particularly in non-vignette conditions when these expressions were void of context. These findings suggest that closeness does indeed facilitate emotional perception, particularly in ambiguous situations for negative emotions.


Quantification of biological variation in blood-based therapy--a summary of a meta-analysis to inform manufacturing in the clinic.
Biological raw materials, the basis for cellular therapies such as stem cells, have a significantly greater degree of complexity than their traditional pharmaceutical counterparts. This can be attributed to the inherent variation of its source - human beings. Currently, cell therapies are made in small, ad hoc batches, but larger scale production is a prerequisite to meeting future demand and will require a quality-by-design approach to manufacturing that will be designed around, or be robust to this variation. Quantification of variation will require understanding of the current baseline and stratification of its sources. Haematopoietic stem cell therapy was chosen as a case study to explore this variation, and a PRISMA-guided (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) systematic meta-analysis was carried out for a number of predetermined cell measurements. From this data set, it appears that the extent of variation in therapeutic dose (in terms of transplanted total nucleated cells and CD34(+) cells per kilogram) for HSCT is between one and four orders of magnitude of the median. This is tolerated under the practice of medicine but would be unmanageable from a biomanufacturing perspective and raises concerns about comparable levels of efficacy and treatment. A number of sources that will contribute towards this variation are also reported, as is the direction of travel for 4 greater clarity of the scale of this challenge.


Osmotic Shock Inhibits Auxin-stimulated Acidification and Growth.
Cells of oat coleoptiles (Avena sativa L. cv. "Garry") have been osmotically shocked in order to observe the effect of alterations of the plasma membrane on some auxin responses. When coleoptile sections were treated sequentially with 0.5 m mannitol and 1 mm Na-phosphate (pH 6.4) at 4 C, polar auxin transport and acidification by 1 mM CaCl(2) were unaffected, but auxin-stimulated acidification and growth were eliminated. Shock treatment also had no effect on acid-stimulated growth or on freezing point depression by the cytoplasm. It is suggested that osmotic shock modifies a portion of the plasma membrane which interacts with auxin and eventually leads to growth.


Enriched environment alleviates post-stroke cognitive impairment through enhancing α7-nAChR expression in rats.
Enriched environment (EE) is a simple and effective intervention to improve cognitive function in post-stroke cognitive impairment (PSCI), partly due to the rebalancing of the cholinergic signaling pathway in the hippocampus. α7-nicotinic acetylcholine receptor (α7-nAChR) is a cholinergic receptor whose activation inhibits inflammation and promotes the recovery of neurological function in PSCI patients. However, it is still unclear whether EE can regulate α7-nAChR and activate the cholinergic anti-inflammatory pathway (CAP) in PSCI. To investigate the effects of EE on cognitive impairment, and the role of α7-nAChR in PSCI. A PSCI rat model was induced by middle cerebral artery occlusion and reperfusion (MCAO/R) and were reared in standard environment (SE) or EE for 28d, control group with sham surgery. Cognitive function was determined by Morris water maze test. The long-term potentiation (LTP) was assessed by Electrophysiology. Histopathological methods were used to determine infarct volume, α7-nAChR expression and the cytokines and cholinergic proteins expression. Compared with SE group, rats in EE group had better cognitive function, higher expression of α7-nAChR positive neurons in hippocampal CA1 region. In addition, EE attenuated unfavorable changes induced by MCAO/R in cytokines and cholinergic proteins, and also enhanced LTP promoted by nicotine and attenuated by α-BGT; but showed no significantly difference in infarct volume. EE markedly improves cognitive impairment and enhances neuroplasticity in PSCI rats, which may be closely related to enhancement of α7-nAChR expression.


Multidetector Computed Tomography Angiography Combined with Intravascular Ultrasound for the Evaluation of Coronary Veins for Percutaneous Mitral Annulus Repair Using Transcoronary Sinus Devices.
Multidetector computed tomography angiography (MDCTA) can be used to evaluate the target location of transcoronary sinus devices. This study aimed to assess the accuracy of MDCTA in evaluating the target location of transcoronary sinus devices compared with intravascular ultrasound (IVUS). Forty-two patients planned to undergo mitral valve repair (MVR) were prospectively enrolled at Zhoupu Hospital (China) including 15 with secondary mitral regurgitation (MR) grade ≥3. MDCTA was performed to measure the diameters of coronary sinus ostium (CSO) and proximal anterior interventricular vein (PAIV) and the distance between them. During MVR, these parameters were measured using IVUS before electrode insertion. There was a strong linear correlation between the diameter of CSO measured by MDCTA and IVUS (r = 0.967, P < 0.001), as well as for PAIV (r = 0.954, P < 0.001) and the distance between them (r = 0.986, P < 0.001). No significant differences were found between the results measured by MDCTA and IVUS. The patients with secondary MR grade ≥3 had significantly larger CSO and PAIV measured by IVUS (P = 0.003 and P = 0.017, respectively), as well as by MDCTA (P = 0.010 and P = 0.008, respectively). Dual-source MDCTA might allow the quantitative evaluation of the target location of transcoronary sinus devices with a good accuracy. It may be a good choice for guiding the selection of transcoronary sinus devices.


[Infantile spasms as the first manifestation of propionic acidemia].
Propionic acidemia is a disorder of branch-chain amino acids, the side chain of cholesterol and odd-chain fatty acid metabolism that leads to the accumulation of toxic acid metabolites. The clinical features typically begin shortly after birth, although they can also appear in young adulthood. We report the case of a 3-year-old boy with atypical onset, who at 6 months presented bursts of infantile spasms and a hypsarrhythmic electroencephalogram. He was treated with vigabatrin. At 8 months magnetic resonance imaging showed a wider than normal subarachnoidal space, and hyperintense thalamus, globus pallidus and subthalamic nucleus. Biochemical and genetic analysis confirmed propionic acidemia. Specific therapy was started and the patient is not currently under anti-epileptic treatment and his electroencephalogram is normal. This onset of propionic acidemia is unusual, and we believe that treatment with vigabatrin protected the basal ganglia from irreversible excitotoxic damage.


Screening Practices for Disordered Eating in Paediatric Type 1 Diabetes Clinics.
Type 1 Diabetes (T1D) is associated with increased risk of eating disorders. This study aimed to (1) assess adherence of Australasian paediatric T1D clinics to international guidelines on screening for disordered eating and (2) identify barriers and enablers to the use of screening tools for the identification of disordered eating. A 24-item survey covering five content domains: clinic characteristics, identification of disordered eating, screening tool use, training and competence, and pathways for referral, was sent to Australasian clinics caring for ≥150 children and adolescents with T1D. Of 13 eligible clinics, 10 participated. Two reported rates of disordered eating of >20%, while eight reported rates < 5%. All clinics used the routine clinical interview as the primary method of screening for disordered eating. Only one used screening tools; these were not diabetes-specific or routinely used. Barriers to use of screening tools included shortage of time and lack of staff confidence around use (n = 7, 70%). Enablers included staff training in disordered eating. Screening tools for disordered eating are not utilised by most Australasian paediatric T1D clinics. Overall, low reported rates of disordered eating suggest that it may be undetected, potentially missing an opportunity for early intervention.


Persistent non-cancer pain management in the older adult.
Pain is a prevalent symptom affecting as many as 50% of community-dwelling older adults. Pain affects quality of life, functional status, cognition, mood, sleep, and well-being. A multimodal approach to pain management consists of both non-pharmacologic and pharmacologic interventions. Prescribing analgesics is safe and effective in older persons if done judiciously by starting low and titrating slowly while monitoring closely for potential side effects.


Human periplakin: genomic organization in a clonally unstable region of chromosome 16p with an abundance of repetitive sequence elements.
Periplakin, a member of the plakin family of proteins, has been recently characterized by cDNA cloning, and the corresponding gene, PPL, has been mapped to human chromosome 16p13.3 (Aho et al., 1998, Genomics 48: 242-247). Periplakin has also been shown to serve as an autoantigen in a malignancy-associated autoimmune blistering disease, paraneoplastic pemphigus (Mahoney et al., 1998, J. Invest. Dermatol. 111: 308-313). In this study, we have elucidated the intron-exon organization of human PPL and characterized its promoter region. The flanking 5' sequences were rich in G and C ( approximately 80%) and included multiple AP2 sites and a SP1 site, while no canonical TATA or CCAAT sequences were found. The functionality of the upstream sequences (-709 to +135) as a promoter in cultured epidermal keratinocytes was detected by a CAT reporter gene, and a limited region (-382 to +135) showed activity in cultured dermal fibroblasts, attesting to cell-type specificity of the promoter. The genomic organization, including the intron-exon borders, was determined by direct nucleotide sequencing of human genomic P1 clones. Comparative analysis of cDNA and genomic sequences revealed that PPL consists of 22 exons, with the distribution of exons in PPL being consistent with that of other plakin genes: 21 small exons, separated by large introns, encode the amino-terminal globular domain, and 1 large exon encodes the entire rod and the tail domains. Characterization of four P1 clones spanning the PPL locus revealed multiple Alu repeats, 20 of them within 33 kb of the entirely sequenced segments (0.60/kb), in addition to numerous MIR and L1 elements. These repetitive elements could lead to the clonal instability detected throughout the genomic P1 clones and may give rise to the genomic rearrangements possibly underlying the paraneoplastic pemphigus.


Changes in Soybean (Glycine max [L.] Merr.) Glycerolipids in Response to Water Stress.
Soybean (Glycine max [L.] Merr.) plants with the first trifoliate leaf fully expanded were exposed to 4 and 8 days of water stress. Leaf water potentials dropped from -0.6 megapascal to -1.7 megapascals after 4 days of stress; then to -3.1 megapascals after 8 days without water. All of the plants recovered when rewatered. The effects of short-term drought stress on triacylglycerol, diacylglycerol, phospholipid, and galactolipid metabolism in the first trifoliate leaves was determined. Leaf triacylglycerol and diacylglycerol content increased 2-fold during the first 4 days of stress and returned to control levels 3 days after rewatering. The polar lipid fraction, which contained phospholipids and galactolipids, changed little during this time. The linolenic acid (18:3) content of the triacylglycerol and diacylglycerol increased 25% during stress and the polar lipid 18:3 content decreased 15%. The pattern of glycerolipid labeling, after applying [2-(14)C]acetate to intact leaves was altered by water stress. After 4 days of water stress the radioactivity of phosphatidic acid + phosphatidylinositol, phosphatidylcholine, triacylglycerol, and diacylglycerol increased between 4 and 9% (compared to control plans) while radioactivity of phosphatidylethanolamine, monogalactosyldiglyceride, and digalactosyldiglyceride decreased 2 to 11%. These data indicated that increased levels of triacylglycerol and diacylglycerol observed during water stress were attributed to de novo synthesis rather than breakdown or reutilization of existing glycerolipids and fatty acids.


Control over the Self-Assembly Modes of Pt(II) Complexes by Alkyl Chain Variation: From Slipped to Parallel π-Stacks.
We report the self-assembly of a new family of hydrophobic, bis(pyridyl) Pt(II) complexes featuring an extended oligophenyleneethynylene-derived π-surface appended with six long (dodecyloxy (2)) or short (methoxy (3)) side groups. Complex 2, containing dodecyloxy chains, forms fibrous assemblies with a slipped arrangement of the monomer units (dPt⋅⋅⋅Pt ≈14 Å) in both nonpolar solvents and the solid state. Dispersion-corrected PM6 calculations suggest that this organization is driven by cooperative π-π, C-H⋅⋅⋅Cl and π-Pt interactions, which is supported by EXAFS and 2D NMR spectroscopic analysis. In contrast, nearly parallel π-stacks (dPt⋅⋅⋅Pt ≈4.4 Å) stabilized by multiple π-π and C-H⋅⋅⋅Cl contacts are obtained in the crystalline state for 3 lacking long side chains, as shown by X-ray analysis and PM6 calculations. Our results reveal not only the key role of alkyl chain length in controlling self-assembly modes but also show the relevance of Pt-bound chlorine ligands as new supramolecular synthons.


Guidelines for the care of the patient on home nutrition support. An appendix.
A significant portion of the health care provided in this country has been shifted to the home care environment. As a result, patients are discharged from the hospital earlier, with increased needs for highly skilled care. Much of the daily, hands-on care patients require, is provided by family members or care givers and supported by periodic visits from health care professionals. Home nutrition support is one of the many "technical" therapies that is routinely administered at home. To ensure the success of home nutrition support one must identify appropriate candidates, develop a nutritional plan of care agreeable to the patient/care giver, design a prescription appropriate for the home setting, and properly train the patient/care giver.


Nuclear calcium signalling by individual cytoplasmic calcium puffs.
It is known that the nucleoplasmic ionised calcium concentration (Can) controls nuclear functions such as transcription, although the source and nature of the signals which modulate Can are unclear. Using confocal imaging, we investigated the subcellular origin of Can signals in Fluo-3-loaded HeLa cells. Our data indicate that all signals which increased Can were of cytoplasmic origin. Can was elevated during the propagation of global Ca waves within cells. More strikingly, we found that individual cytoplasmic elementary release events e.g. Ca puffs, evoked by physiological levels of stimulation, caused transient Can increases. Significantly, >70% of all Ca puffs originated within a 2-3 micron perinuclear zone and propagated anisotropically across the entire nucleus. Due to the relatively slow relaxation of Can transients compared with those in the cytoplasm, repetitive perinuclear Ca puffs were integrated into a 'staircase' of increasing Can. Due to the effective diffusion of Ca in the nucleoplasm, the nucleus served as a 'Ca tunnel', distributing Ca to parts of the cytosol which were otherwise not within the cytoplasmic diffusion radii of Ca puffs. Given the close proximity of the majority of puff sites to the nucleus, it seems that the elementary Ca release system is designed to facilitate nuclear Ca signalling. Consequently, Ca-dependent regulation of nuclear function must be considered at the microscopic elementary level.


[[Demographic data and spline interpolation]].
Five formulas of spline interpolation and their applications to demographic data are introduced. "The formulas are applied to (1) interpolating and smoothing values of life table functions....(2) interpolating births by five-year age groups of mothers into single ages....(3) interpolating cause-specific deaths by five-year age groups into single ages....[and] (4) interpolating and smoothing two-dimensional demographic data e.g. mortality rates and expectations of life by year and age." (SUMMARY IN ENG)


Mid- to long-term outcomes of a medial-pivot system for primary total knee replacement: a systematic review and meta-analysis.
This systematic review and meta-analysis was conducted to determine the mid- to long-term clinical outcomes for a medial-pivot total knee replacement (TKR) system. The objectives were to synthesise available survivorship, Knee Society Scores (KSS), and reasons for revision for this system. A systematic search was conducted of two online databases to identify sources of survivorship, KSS, and reasons for revision. Survivorship results were compared with values in the National Joint Registry of England, Wales, and Northern Ireland (NJR). A total of eight studies that included data for 1146 TKRs performed in six countries satisfied the inclusion/exclusion criteria. Pooled component survivorship estimates were 99.2% (95% CI, 97.7 to 99.7) and 97.6% (95% CI, 95.8 to 98.6) at five and eight years, respectively. Survivorship was similar or better when compared with rates reported for all cemented TKRs combined in the NJR and was significantly better than some insert types at mid-term intervals. The weighted mean post-operative KSS was 87.9 (73.2 to 94.2), in the excellent range. Similar cumulative revision rates and KSS were reported at centres in the United States, Europe, and Asia. The subject system was associated with survivorship and KSS similar or better than that reported for other TKR systems. Cite this article: Bone Joint Res 2014;3:297-304.


Synthesis and cytotoxic activity of acronycine analogues in the benzo[c]pyrano[3,2-h]acridin-7-one and naphtho[1,2-b][1,7] and [1,10]-phenanthrolin-7(14H)-one series.
Condensation of 1-bromo-2-naphthalenecarboxylic acid (9) with 7-methoxy-2,2-dimethyl-2H-1-benzopyran-5-ylamine (13) followed by acid-mediated cyclization afforded 6-methoxy-3,3-dimethyl-3,14-dihydro-7H-benzo[c]pyrano[3,2-h]acridin-7-one (15), which was further methylated into 6-methoxy-3,3,14-trimethyl-3,14-dihydro-7H-benzo[c]pyrano[3,2-h]acridin-7-one (benzo[c]acronycine) (3) and 6,7-dimethoxy-3,3-dimethyl-3H-benzo[c]pyrano[3,2-h]acridine (4). Osmium tetroxide oxidation of 15 gave the (+/-)-cis-diol 16, which afforded the benzopyranoacridine and benzopyranoacridone esters 17-22 upon acylation. Condensation of 9 with suitable aminoquinolines 23-25 afforded the carboxylic naphthylquinolylamines 26-28. Cyclization gave the corresponding naphtho[1,2-b][1,10]-phenanthrolin-7(14H)-ones 29 and 30, and naphtho[1,2-b][1,7]-phenanthrolin-7(14H)-one 31, which were subsequently N-methylated to the desired 14-methylnaphtho[1,2-b][1,10] and [1,7]-phenanthrolinones 6, 7, and 8. Benzo[c]pyrano[3,2-h]acridin-7-one derivatives 3, 16, and 22 displayed cytotoxic activities within the same range of magnitude as acronycine itself, whereas 7-alkoxybenzo[c]pyrano[3,2-h]acridine and 7-acyloxybenzo[c]pyrano[3,2-h]acridine derivatives 4 and 17-21 were less active when tested against L1210 murine leukemia cells in vitro. Naphthophenanthrolinones 6-8 were devoid of significant antiproliferative activity, but compounds 29-31 bearing no substituent on the nitrogen atom at position 14 were more potent.


Antibodies against hepatitis C virus (anti-HCV) in haemodialysis patients: association with hepatitis B serological markers.
Hepatitis C virus (HCV) seems to be the main causative agent of the parenterally transmitted non-A, non-B hepatitis and the detection of anti-HCV may be a marker of ongoing infection with this virus. This study was undertaken to determine the frequency of anti-HCV in 51 haemodialysis patients of our renal unit. In addition association of these antibodies to sex, history of blood transfusions, and duration on haemodialysis, as well as to serological markers of hepatitis B virus infection, was applied. Enzyme-linked immunosorbent assay (ELISA), were used for the detection of all serological markers. Nine of the 51 (17.6%) haemodialysis patients had anti-HCV. The presence of anti-HCV was related to male sex. Although seropositive patients were transfused more often than seronegatives, this difference is not statistically significant. The presence of anti-HCV was associated with the duration of haemodialysis. The majority of anti-HCV patients had serological markers of previous HBV infection, in contrast to seronegative patients.


Optimized electroporation of CRISPR-Cas9/gRNA ribonucleoprotein complex for selection-free homologous recombination in human pluripotent stem cells.
Selection-free, scarless genome editing in human pluripotent stem cells (PSCs) by utilizing ribonucleoprotein (RNP) of CRISPR-Cas9 is a useful tool for a variety of applications. However, the process can be hampered by time-consuming subcloning steps and inefficient delivery of the RNP complex and ssDNA template. Here, we describe the optimized protocol to introduce a single nucleotide change or a loxP site insertion in feeder-free, xeno-free iPSCs by utilizing MaxCyte and 4D-Nucleofector electroporators. For complete details on the use and execution of this protocol, please refer to Kagita et al. (2021) and Xu et al. (2019).


G1 is the major APOL1 risk allele for hypertension-attributed nephropathy in Central Africa.
Sub-Saharan Africans exhibit a higher frequency of chronic kidney disease (CKD) than other populations. In this study, we sought to determine the frequency of apolipoprotein L1 (APOL1) genotypes in hypertension-attributed CKD in Kinshasa, Democratic Republic of the Congo. We performed a case-control study identifying 162 subjects: 79 with hypertension-attributed CKD and 83 controls living in Kinshasa who were genotyped for APOL1 risk variants between July 2013 and November 2016. We selected control subjects from the general population and matched them with the cases according to age. Logistic regression analysis was used to examine the relationship between APOL1 high-risk genotypes and CKD. The frequencies of the APOL1 G1 and G2 alleles were 19.1 and 7.1%, respectively. The number of individuals with the G1 and G2 risk alleles was significantly higher in the CKD group (12.7%) than in the control group (2.4%), particularly in individuals with end-stage kidney disease (14.3%). Subjects carrying two risk alleles was strongly and independently associated with hypertension-attributed nephropathy, with an adjusted odds ratio of 7.7 (95% confidence interval 1.5-39.7; P = 0.014). The high-risk APOL1 genotypes were G1/G1 and G1/G2, whereas G2/G2 was not found in the study population. The results of this study demonstrate the association of high-risk APOL1 genotypes with kidney disease in Kinshasa. The absence of G2/G2 may be consistent with powerful selective sweeps induced by Trypanosoma brucei gambiense infection. In contrast, the presence of APOL1 G2/G2 among individuals of African ancestry in the USA may indicate relaxation of natural selection in a trypanosome-free environment.


The heritability of preterm delivery.
To study the heritability of preterm delivery. Women who delivered a singleton infant at less than 36 weeks of gestation were asked about their family history. Twenty-eight families were identified in which the proband had at least five first- or second-degree relatives with preterm delivery. An extensive genealogy database (GenDB) was constructed using more than 9,000 genealogy sources in the public domain (records before 1929). GenDB documents the relationships between more than 17.5 million ancestors and 3.5 million descendants of approximately 10,000 individuals who moved to Utah in the mid 1800s. This database was searched for the names, birth dates, and birthplaces of the four grandparents for each of the 28 probands. Pairwise coefficients of kinship were determined for the 93 preterm delivery grandparents identified, and for sets of 100 individuals born in the 1920s who were randomly selected from the population database. Probands had a mean of 3.3 grandparents included in this database. The average coefficient of kinship for controls was 1.5 x 10(6) (standard deviation = 0.6 x 10(6)). This measure agrees with previous calculations for the Utah population. The coefficient of kinship for familial preterm delivery grandparents was more than 50 standard deviations higher (3.4 x 10(5) [P < .001]). This study confirms the familial nature of preterm delivery. On average, gravidae randomly selected from our population are 23rd degree relatives, while these preterm delivery probands are eighth-degree relatives. A genome-wide scan using these affected families is underway.