Position statement for adult and paediatric spirometry in South Africa: 2022 update.
Spirometry is required as part of the comprehensive evaluation of both adult and paediatric individuals with suspected or confirmed respiratory diseases and occupational assessments. It is used in the categorisation of impairment, grading of severity, assessment of potential progression and response to interventions. Guidelines for spirometry in South Africa are required to improve the quality, standardisation and usefulness in local respiratory practice. The broad principles of spirometry have remained largely unchanged from previous versions of the South African Spirometry Guidelines; however, minor adjustments have been incorporated from more comprehensive international guidelines, including adoption of the Global Lung Function Initiative 2012 (GLI 2012) spirometry reference equations for the South African population. All equipment should have proof of validation regarding resolution and consistency of the system. Daily calibration must be performed, and equipment quality control processes adhered to. It is important to have standard operating procedures to ensure consistency and quality and, additionally, strict infection control as highlighted during the COVID-19 pandemic. Adequate spirometry relies on a competent, trained operator, accurate equipment, standardised operating procedures, quality control and patient co-operation. All manoeuvres must be performed strictly according to guidelines, and strict quality assurance methods should be in place, including acceptability criteria (for any given effort) and repeatability (between efforts). Results must be categorised and graded according to current guidelines, taking into consideration the indication for the test.


Cyclic fatigue resistances of Hyflex EDM, WaveOne gold, Reciproc blue and 2shape NiTi rotary files in different artificial canals.
The aim of the present study was to compare the cyclic fatigue resistances of HyFlex EDM (HEDM), WaveOne Gold (WOG), Reciproc Blue (RB), and 2Shape (TS) NiTi systems having different metallurgic properties. HEDM, WOG, RB, and TS instruments were rotated in artificial canals which were made of stainless steel with an inner diameter of 1.5 mm, 45°, and 90° angles of curvatures and a radius of curvature of 5 mm until fracture occurred, and the time to fracture (TTF) was recorded in seconds. Also, number of cycles to fracture was calculated (NCF). Data were statistically analyzed using Kruskal-Wallis and t test. The statistical significance level was set at P < 0.05. When comparing the TTF of all the instruments tested in the artificial canal with 45° curvature, RB had statistically the highest cyclic fatigue resistance followed by HEDM and TS (P < 0.05), while the WOG showed the lowest cyclic fatigue resistance (P < 0.05). In artificial canal with 90° curvature, RB showed a significantly higher cyclic fatigue resistance than the other tested files (P < 0.05), while there was no significant difference among the TS, WOG and HEDM groups (P > 0.05). When the NCF values were taken into consideration, HEDM reported a significantly higher cyclic fatigue resistance than TS in both canal curvatures analyzed (P < 0.05). Within the limitations of the present study, RB NiTi files showed statistically higher cyclic fatigue resistance in artificial canals with 45° and 90° than the other NiTi files tested.


Comparison of super-mini PCNL (SMP) versus Miniperc for stones larger than 2 cm: a propensity score-matching study.
To compare the efficacy and safety of Super-mini percutaneous nephrolithotomy (SMP, F12-F14) and Miniperc (F18) in the treatment of renal stones of 2-4 cm in size. A prospective comparative analysis of outcomes of patients who underwent SMP and Miniperc for treatment of 2-4 cm renal stones was conducted between July 2014 and January 2017. Demographic data, stone criteria, operative technique, complications, blood transfusion, hemoglobin decrease, stone-free rate (SFR) and length of hospital stay were compared between the two groups. Propensity score-matching (PSM) analysis was performed to further compare the outcomes between the two groups. 79 and 257 patients underwent SMP and Miniperc, respectively. After matching, 73 patients in each group were included. The stone burden was comparable for both groups (3.0 ± 1.1 vs 3.2 ± 0.7 cm, p = 0.577). Mean operation time was not significant different between two groups (p = 0.115), while the hospital stay of SMP was much shorter than Miniperc (2.6 ± 1.4 vs 5.2 ± 1.8, p < 0.0001). Both groups had similar SFRs in postoperative 1 day and at 1 month follow-up (p = 0.326, p = 0.153), while SMP achieved a markedly higher tubeless rate than Miniperc (84.9 vs 47.9%, p < 0.0001). The total complication rate was significantly lower in SMP (16.4 vs 41.1%, p = 0.0001), and the SIRS rate was markedly lower in SMP group (1.4 vs 12.3%, p = 0.009). SMP is equally effective as Miniperc in the treatment of moderate renal calculi, and has the significant advantage in hospital duration and tubeless rate.


Long working hours, occupational health and the changing nature of work organization.
The impact of long working hours on health has been of major concern since the late 19th Century. Working hours are again increasing in the US. An overview of historical, sociological, and health-related research presented at an international conference on long working hours is discussed as an introduction to a special section in this issue. Research indicates that long working hours are polarizing along class lines with professionals working regular though longer hours and less well-educated workers having fewer though more irregular hours. Extended and irregular hours are associated with acute reactions such as stress and fatigue, adverse health behavior such as smoking, and chronic outcomes such as cardiovascular and musculoskeletal disorders. Improved methodologies are needed to track exposure to long working hours and irregular shifts longitudinally. Research should focus on the adverse impact that sleep-deprived and stressed workers may have on the health of the public they serve. A variety of protective efforts should be undertaken and evaluated.


The effect of combat-related posttraumatic stress disorder on the family.
This paper reviews literature on the detrimental effect of combat-related posttraumatic stress disorder on the family. The literature indicates that guilt feelings, emotional withdrawal and elevated levels of aggression in the returning veteran make it difficult, perhaps even impossible, for him to fully resume his former roles of father, husband and breadwinner. Wives and children of veterans show psychiatric symptoms. Despite these hardships, the families are generally reluctant to seek professional help. The clinical implications are discussed and suggestions are made for intervention and outreach.


[Effects of tongue acupuncture combined with rehabilitation training group of dysarthria on speech function in post-stroke dysarthria patients].
To observe the effects of tongue and nape acupuncture combined with rehabilitation training group of dysarthria on speech function in post-stroke dysarthria patients, and to explore the treatment of dysarthria. Eighty patients with dysarthria were randomly divided into an observation group (40 cases) and a control group (40 cases). The patients in the two groups were treated with conventional treatment. The patients in the control group were treated with the acupuncture combined with rehabilitation training group of dysarthria; the patients in the observation group were treated with the control group treatment and tongue acupuncture, once a day, 6 days per week for 2 weeks. The patients were evaluated with general dysarthria scale and dysarthria checklist of Chinese Rehabilitation Study Center before and after 2-week treatment. After treatment, the total score and each item score of general dysarthria scale were reduced (all P<0.05); all the score in the observation group was lower than those in the control group (all P<0.05), except the score of jaw which had no significant difference between the two groups. After treatment, the dysarthria checklist of Chinese Rehabilitation Study Center in the observation group was superior to that in the control group (P<0.05). The total effective rate was 85.0% (34/40) in the observation group, which was higher than 67.5% (27/40) in the control group (P<0.05). Tongue acupuncture, nape acupuncture and rehabilitation training group of dysarthria could effectively improve the speech function of post-stroke dysarthria patients.


Ultra-wide optical coherence tomography angiography in diabetic retinopathy.
To implement an ultra-wide optical coherence tomography angiography imaging (UW-OCTA) modality in eyes with diabetic retinopathy (DR) with the aim of quantifying the burden of microvascular disease at baseline and subsequent clinic visits. UW-OCTA was implemented on a 1,060 nm swept source (SS) OCTA engine running at 100 kHz A-line rate with a motion tracking mechanism. A montage scanning protocol was used to capture a 100-degree field of view (FOV) using a 4×4 grid of sixteen total individual 6×6 mm2 scans. Typical OCTA images with a FOV of 3×3, 6×6 and 12×12 mm2 were obtained for comparison. DR patients were scanned at baseline and follow-up. They were treated at the clinician's discretion. Vessel density and non-perfusion area maps were calculated based on the UW-OCTA images. Three proliferative DR patients were included in the study. UW-OCTA images provided more detailed visualization of vascular networks compared to 50-degree fluorescein angiography (FA) and showed higher burden of pathology in the retinal periphery that was not captured by typical OCTA. Neovascularization complexes were clearly detected in the two patients with active PDR. Vessel density and non-perfusion maps were used to measure progressive capillary non-perfusion and regression of neovascularization between visits. UW-OCTA provides approximately 100-degree OCTA images of the fundus comparable to that of wide-angle fundus photography, and may be more applicable in conditions such as DR which affect the peripheral retina in contrast to standard OCTA.


Morphological and phylogenetic analyses reveal two new species in Conidiobolus s.s. (Conidiobolaceae, Entomophthorales) from China.
The genus Conidiobolus s.s. (Conidiobolaceae, Entomophthorales) has been delimited to accommodate members that produce microspores. Herein, morphological studies, combined with phylogenetic analysis based on the nuclear large subunit of rDNA (nucLSU), the mitochondrial small subunit of rDNA (mtSSU), and the elongation-factor-like gene (EFL) revealed two Conidiobolus s.s. species isolated from plant debris in China. Conidioboluslongiconidiophorussp. nov. is mainly characterised by its long primary conidiophores, while Conidioboluspolysporussp. nov. is diagnosed by 2-3 primary conidia arising from branched primary conidiophores. Phylogenetically, the former is grouped into a separate clade, while the latter is closely related to C.incongruus, but is morphologically distinguished by its larger primary conidia and branched conidiophores.


Risk factors associated with an outbreak of equine coronavirus at a large farm in North Carolina.
Equine coronavirus (ECoV) leads to outbreaks with variable morbidity and mortality. Few previous reports of risk factors for infection are available in the literature. To describe unique clinical findings and risk factors for infection and development of clinical disease. 135 horses on a farm affected by ECoV outbreak. Retrospective cohort study. Data obtained included age, breed, gender, activity level, housing, and feed at the onset of the outbreak. Factors were evaluated for assessment of risk of infection using simple logistic regression or Fisher's exact test. Significance was set at p ≤ 0.05. Forty-three of 54 (79.6%) horses tested on the farm were positive on fecal PCR for ECoV, and 17 horses (12.6%) developed clinical signs consistent with ECoV. Out of 17 horses in which the presence or absence of signs of colic was noted, 6 of 17 (35.3%) showed signs of colic. Three of these horses had small colon impactions, 2 of which required surgical intervention. Significant risk factors for having positive PCR results included being primarily stalled (OR 167.1, 95% CI 26.4-1719), housing next to a positive horse (OR 7.5, 95% CI 3.1-19.0), being in work (OR 26.9, 95% CI 4.6-281.9), being fed rationed hay vs. ad libitum (OR 1,558, 95% CI 130.8-15,593), and being fed alfalfa hay (OR 1,558, 95% CI 130.8-15,593). This report describes risk factors for ECoV infection many of which were associated with intensive management of show horses. Clinicians should be aware that clinical signs vary and can include severe colic.


Reliability of lower extremity muscle strength measurements with handheld dynamometry in stroke patients during the acute phase: a pilot reliability study.
[Purpose] No literature has described a suitable method for measuring muscle strength in a supine position during acute phase after stroke. This study investigated the feasibility and reliability of using a commercial handheld dynamometer to measure the muscle strengths of the hip flexor, knee extensor, and dorsiflexor in the supine position with a modified method for patients at a stroke intensive care center within 7 days of stroke onset. [Subjects and Methods] Fifteen persons with acute stroke participated in this cross-sectional study. For each patient, the muscle strengths of the hip flexors, knee extensors, and dorsiflexors were measured twice by two testers on the same day. Each patient was re-tested at the same time of day one day later. Inter-rater and test-retest reliability were then determined by the intraclass correlation coefficients (ICCs). [Results] For the three muscle groups, the inter-rater reliability ICCs were all 0.99 and the test-retest reliability ICCs were greater than 0.85. The investigated method thus has good inter-rater reliability and high agreement between the test-retest measurements, with acceptable measurement errors. [Conclusion] The modified method using a handheld dynamometer to test the muscle strength of acute stroke patients is a feasible and reliable method for clinical use.


Mood Dimensions Show Distinct Within-Subject Associations With Non-exercise Activity in Adolescents: An Ambulatory Assessment Study.
Physical activity is known to preserve both physical and mental health. However, the physical activity levels of a large proportion of adolescents are insufficient. This is critical, since physical activity levels in youth have been shown to translate into adulthood. Whereas in adult populations, mood has been supposed to be one important psychological factor that drives physical activity in everyday life, this issue has been poorly studied in adolescent populations. Ambulatory Assessment is the state-of-the-art approach to investigate how mood and non-exercise activity fluctuate within persons in everyday life. Through assessments in real time and real life, this method provides ecological validity, bypassing several limitations of traditional assessment methods (e.g., recall biases). To investigate whether mood is associated with non-exercise activity in adolescents, we equipped a community-based sample comprising 113 participants, aged 12-17 years, with GPS-triggered e-diaries querying for valence, energetic arousal, and calmness, and with accelerometers continuously measuring physical activity in their everyday lives for 1 week. We excluded all acceleration data due to participants' exercise activities and thereafter we parameterized non-exercise activity as the mean value across 10-min intervals of movement acceleration intensity following each e-diary prompt. We used multilevel analyses to compute the effects of the mood dimensions on non-exercise activity within 10-min intervals directly following each e-diary prompt. Additionally, we conducted explorative analyses of the time course of the effects, i.e., on different timeframes of non-exercise activity up to 300 min following the mood assessment. The results showed that valence (p < 0.001) and energetic arousal (p < 0.001) were positively associated with non-exercise activity within the 10 min interval, whereas calmness (p < 0.001) was negatively associated with non-exercise activity. Specifically, adolescents who felt more content, full of energy, or less calm were more physically active in subsequent timeframes. Overall, our results demonstrate significant associations of mood with non-exercise activity in younger ages and converge with the previously observed association between mood and physical activity in adults. This knowledge on distinct associations of mood-dimensions with non-exercise activity may help to foster physical activity levels in adolescents.


5,5-Dimethyl-2-[6-methyl-2-(methylsulfanyl)pyrimidin-4-yloxy]-1,3,2-dioxaphosphorinane-2-thione.
The title compound, C(11)H(17)N(2)O(3)PS(2), is a cyclic thiophosphoryl pyrimidine derivative exhibiting insecticidal properties. The crystal structure determination gives evidence for the presence of the thione isomer of the compound. The pyrimidine nucleus is planar and its substituents have small deviations from the least-squares plane. The dioxaphosphorinane ring adopts a chair conformation. The lack of classical hydrogen bonds and the weak intermolecular interactions lead to a 'loose' packing characterized by channels in the structure.


Incidence and prevalence of falls in adults with intellectual disability living in the community: a systematic review protocol.
The objective of this review is to synthesize the best available evidence to determine the incidence and prevalence of falls in adults with intellectual disability living in the community.


Elks Lodge building collapse.
Of the 50 patients we anticipated, we evaluated 14 victims, two firefighters and two people in the crowd who developed anxiety-related symptoms in reaction to the incident. Forty-eight people escaped the building in various ways, with the most amazing being when rubble created a hole in the wall that led to a stairwell where people were able to get out. We transported 11 patients to the local hospital, four were flown to trauma centers in Kansas City, and four refused to be transported. Of those four, one later went to the ED, where he was diagnosed as having an AMI and was flown to a cardiac center in Kansas City.


Electroencephalogram Burst-suppression during Cardiopulmonary Bypass in Elderly Patients Mediates Postoperative Delirium.
Intraoperative burst-suppression is associated with postoperative delirium. Whether this association is causal remains unclear. Therefore, the authors investigated whether burst-suppression during cardiopulmonary bypass (CPB) mediates the effects of known delirium risk factors on postoperative delirium. This was a retrospective cohort observational substudy of the Minimizing ICU [intensive care unit] Neurological Dysfunction with Dexmedetomidine-induced Sleep (MINDDS) trial. The authors analyzed data from patients more than 60 yr old undergoing cardiac surgery (n = 159). Univariate and multivariable regression analyses were performed to assess for associations and enable causal inference. Delirium risk factors were evaluated using the abbreviated Montreal Cognitive Assessment and Patient-Reported Outcomes Measurement Information System questionnaires for applied cognition, physical function, global health, sleep, and pain. The authors also analyzed electroencephalogram data (n = 141). The incidence of delirium in patients with CPB burst-suppression was 25% (15 of 60) compared with 6% (5 of 81) in patients without CPB burst-suppression. In univariate analyses, age (odds ratio, 1.08 [95% CI, 1.03 to 1.14]; P = 0.002), lowest CPB temperature (odds ratio, 0.79 [0.66 to 0.94]; P = 0.010), alpha power (odds ratio, 0.65 [0.54 to 0.80]; P < 0.001), and physical function (odds ratio, 0.95 [0.91 to 0.98]; P = 0.007) were associated with CPB burst-suppression. In separate univariate analyses, age (odds ratio, 1.09 [1.02 to 1.16]; P = 0.009), abbreviated Montreal Cognitive Assessment (odds ratio, 0.80 [0.66 to 0.97]; P = 0.024), alpha power (odds ratio, 0.75 [0.59 to 0.96]; P = 0.025), and CPB burst-suppression (odds ratio, 3.79 [1.5 to 9.6]; P = 0.005) were associated with delirium. However, only physical function (odds ratio, 0.96 [0.91 to 0.99]; P = 0.044), lowest CPB temperature (odds ratio, 0.73 [0.58 to 0.88]; P = 0.003), and electroencephalogram alpha power (odds ratio, 0.61 [0.47 to 0.76]; P < 0.001) were retained as predictors in the burst-suppression multivariable model. Burst-suppression (odds ratio, 4.1 [1.5 to 13.7]; P = 0.012) and age (odds ratio, 1.07 [0.99 to 1.15]; P = 0.090) were retained as predictors in the delirium multivariable model. Delirium was associated with decreased electroencephalogram power from 6.8 to 24.4 Hertz. The inference from the present study is that CPB burst-suppression mediates the effects of physical function, lowest CPB temperature, and electroencephalogram alpha power on delirium.


Natural killer T-cell characterization through gene expression profiling: an account of versatility bridging T helper type 1 (Th1), Th2 and Th17 immune responses.
Natural killer T (NKT) cells constitute a distinct lymphocyte lineage at the interface between innate and adaptive immunity, yet their role in the immune response remains elusive. Whilst NKT cells share features with other conventional T lymphocytes, they are unique in their rapid, concomitant production of T helper type 1 (Th1) and Th2 cytokines upon T-cell receptor (TCR) ligation. In order to characterize the gene expression of NKT cells, we performed comparative microarray analyses of murine resting NKT cells, natural killer (NK) cells and naïve conventional CD4+ T helper (Th) and regulatory T cells (Treg). We then compared the gene expression profiles of resting and alpha-galactosylceramide (alphaGalCer)-activated NKT cells to elucidate the gene expression signature upon activation. We describe here profound differences in gene expression among the various cell types and the identification of a unique NKT cell gene expression profile. In addition to known NKT cell-specific markers, many genes were expressed in NKT cells that had not been attributed to this population before. NKT cells share features not only with Th1 and Th2 cells but also with Th17 cells. Our data provide new insights into the functional competence of NKT cells which will facilitate a better understanding of their versatile role during immune responses.


NiYAl-Derived Nanoporous Catalysts for Dry Reforming of Methane.
Dry reforming of methane can be used for suppressing the rapid growth of greenhouse gas emissions. However, its practical implementation generally requires high temperatures. In this study, we report an optimal catalyst for low-temperature dry reforming of methane with high carbon coking resistance synthesized from NiYAl alloy. A facile two-step process consisting of preferential oxidation and leaching was utilized to produce structurally robust nanoporous Ni metal and Y oxides from NiYAl4. The catalyst exhibited an optimal carbon balance (0.96) close to the ideal value of 1.0, indicating the optimized dry reforming pathway. This work proposes a facile route of the structural control of active metal/oxide sites for realizing highly active catalysts with long-term durability.


Seeking mental health care from private health practitioners among individuals with alcohol dependence/abuse; results from a study in the French general population.
Better knowledge of the factors that have an impact on pathways to mental health care may contribute greatly to organizing optimum health-care delivery. However, surveillance systems concerning alcohol problems in the French general population are suboptimal. The objectives of this study were to investigate: 1) the prevalence of mental health-care seeking in individuals with alcohol abuse/dependence in France, 2) which category of medical practitioner was consulted, and 3) psychological and socio-environmental factors associated with mental health-care seeking. A total sample of 22,138 individuals was interviewed in a telephone survey. Individual data on alcohol dependence/abuse and other mental health disorders were collected using the Composite International Diagnosis Interview - short form. Mental health-care seeking was assessed, together with data on living conditions, deprivation, and self-reported drinking problems. Only respondents meeting criteria for alcohol dependence/abuse were included in analyses. Less than half of the 722 respondents with alcohol abuse/dependence had sought mental health care in the preceding 12 months, of whom 90.5% consulted their general practitioner (GP) (56.1%), or both a general practitioner and a psychiatrist (34.4%). Mental health-care seeking was associated with female sex, previous alcohol discussion with a doctor, and the presence of psychiatric comorbidities arising in the preceding 12 months. Living environment, socio-economic status, or self-reported drinking problems had no influence. A minority of people with alcohol abuse/dependence sought mental health care, mainly in relation to psychiatric comorbidities. In addition, most people consulting a GP were not referred to a psychiatrist. However, social deprivation and living in rural areas did not hinder mental health-care seeking among respondents. Adequate protocols to treat alcohol disorders could be implemented among private health-care providers to improve management of alcohol problems in France.


Collaborative authoring of biomedical terminologies using a semantic Wiki.
To be broadly useful, biomedical terminologies need to capture the knowledge and expertise of multiple experts, research groups and end users. Consequently, the construction of such a terminology requires collaboration among multiple participants. This paper summarizes several terminology projects which employ a collaborative authoring mode in development, along with the various tools used by these projects to support collaboration, such as mailing list, issue tracking system, client-side GUI software and Wiki system. We then discuss the essential functional requirements for a collaborative authoring tool in the context of terminology development, and analyze the inherent features of Semantic Wiki that enable it to be a competent tool used in this type of effort. To demonstrate, we describe a prototype system of collaborative authoring for health care terminologies built upon the Semantic Wiki technology. Finally, we discuss the potential issues that might be associated with this open Semantic Wiki platform.


Effects of gender identity on experiences of healthcare for sexual minority women.
While research examining healthcare experiences of sexual minority individuals is growing, thus far research has been limited on lesbian gender identity and its relationship to physical and mental health. This study explores access to and experiences of healthcare with a sample of 516 butch and femme identified lesbian and bisexual women. In comparison to femme-identified women, it was found that butch women had routine gynecological examinations significantly less frequently, perceived poorer treatment in healthcare settings, were more likely to be out within healthcare settings, placed more importance on securing LGBT-positive healthcare practitioners, and had more difficulty finding LGBT-positive medical doctors. No differences were found for mental health. The results suggest that butch women may be more at risk for physical health concerns than femme women, in particular those illnesses that can be prevented or treated with regular gynecological care (e.g., uterine or cervical cancer). Implications of the study include greater awareness among healthcare professionals of sexual minority gender identity in addition to sexual identity, and more support for butch-identified women to access vital healthcare services.


Lead equivalence in glass: the default value vs. a defined value.
To most health physicists, the specification of lead-equivalent thickness in a glass viewing window is a request for equal attenuation by the glass and sheet lead of the same stated thickness. A failure to specify the energy at which equivalence is desired can lead to a significant deviation from the intended attenuation value. The reason for this is an alternative or "default" definition of lead equivalence that is used by the glass suppliers when the energy information is omitted.


Aortic smooth muscle relaxants KMUP-3 and KMUP-4, two nitrophenylpiperazine derivatives of xanthine, display cGMP-enhancing activity: roles of endothelium, phosphodiesterase, and K+ channel.
The cellular mechanisms of vasorelaxant effects of newly synthesized KMUP-3 and KMUP-4 were investigated in rat aortic smooth muscle (RASM). KMUP-3 (7-[2-[4-(4-nitrobenzene)piperazinyl]ethyl]-1,3-dimethylxanthine) and KMUP-4 (7-[2-[4-(2-nitrobenzene)piperazinyl]ethyl]-1,3-dimethylxanthine) elicited concentration-dependent relaxation of endothelium-intact and denuded RASM precontracted with phenylephrine. Relaxant responses were also produced by the PDE inhibitors theophylline, milrinone, rolipram, and zaprinast (1 nM-100 microM). The relaxant responses of KMUP-3 and KMUP-4 were reduced by endothelium removal and by the presence of the NOS inhibitor L-NAME (100 microM), the sGC inhibitor ODQ (1 microM), the adenylyl cyclase (AC) inhibitor SQ 22536 (100 microM), and the prostaglandin inhibitor indomethacin (10 microM). Additionally, the vasorelaxations of both agents were also attenuated by pretreatment with the nonselective K+ channel blocker TEA (10 mM), the KATP channel blocker glibenclamide (1 microM), the voltage-dependent K+ (KV) channel blocker 4-AP (100 microM), and Ca(2+)-dependent K+ (KCa) channel blockers apamin (1 microM) and charybdotoxin (ChTX, 0.1 microM). In addition, elevated extracellular K+ (80 mM) interferes with KMUP-3- and KMUP-4-induced vasorelaxations. Preincubation with both agents (1 microM) significantly enhanced the dilator responses of isoproterenol and SNP. KMUP-3 and KMUP-4 inhibited PDE activities and increased cAMP and cGMP levels in primary culture of RASM that were inhibited by SQ 22536 and ODQ, respectively. In cultured HUVECs, KMUP-3 and KMUP-4 (0.1 microM), more potent than YC-1, significantly increased the expression of eNOS protein. In summary, KMUP-3 and KMUP-4 induce aortic relaxations through both endothelium-dependent and -independent mechanisms. Mechanisms of vasorelaxation induced by both compounds involve multiple processes, such as accumulation of cyclic nucleotides partly as a result of PDE inhibition, K-channel activation, and indomethacin-sensitive endothelium function.


What Hath Allah Wrought? The Global Invention of Prescriptive Machines for the Islamic Consumer, 1975-2010.
Unlike histories emphasizing conflicts between religion and technology, this article brings to light a series of religio-technological innovations. It analyzes a dataset of international patents inspired by the practice of Islam, from the first electronic Islamic wristwatch to "The Muslim Xbox." Starting in the 1970s with a few Euro-Muslim inventions, incremental innovations addressing the "needs" of devout Muslims grew exponentially over the course of three decades as inventors from the United States to China aimed to profit from an Islamic revival and emerging "Islamic market." These inventors' devices are described here as "prescriptive machines," arguably designed not for religious flexibility but rather as disciplining mechanisms to train imagined Muslim consumers to conform to a version of orthopraxy. The article ends with an appendix explaining the methodology of researching massive international and multilingual digital databases to establish the dataset of ostensibly "Islamic" patents.


Catalytic properties of the plant cytochrome P450 CYP73 expressed in yeast. Substrate specificity of a cinnamate hydroxylase.
The catalytic properties of CYP73, a cinnamate 4-hydroxylase isolated from Helianthus tuberosus tuber [Teutsch, H. G., Hasenfratz, M. P., Lesot, A., Stoltz, C., Garnier, J. M., Jeltsch, J. M., Durst, F. & Werck-Reichhart, D. (1993) Proc. Natl Acad. Sci. USA 90, 4102-4106] and expressed in an optimised yeast system [Urban, P., Werck-Reichart, D., Teutsch, G. H., Durst, F., Regnier, S., Kazmaier, M. & Pompon, D. (1994) Eur. J. Biochem. 222, 843-850] have been investigated. Microsomes from transformed yeast catalysed trans-cinnamate hydroxylation with high efficiency. CYP73 was highly specific for its natural substrate, and did not catalyse oxygenation of p-coumarate, benzoate, ferulate, naringenin or furanocoumarins. No metabolism of terpenoids or fatty acids, known substrates of plant P450s, was observed. CYP73 however demethylated the natural coumarin herniarin into umbelliferone. In addition, it was shown to oxygenate five xenobiotics and mechanism-based inactivators, including the herbicide chlorotoluron. All substrates of CYP73 were small planar aromatic molecules. Comparison of the kinetic parameters of CYP73 for its various substrates showed that, as expected, cinnamate was by far the best substrate of this P450. The physiological and toxicological significance of these observations are discussed.


Active extravasation of arterial contrast agent on post-traumatic abdominal computed tomography.
To evaluate the use of emergent dynamic intravenous contrast-enhanced computed tomography (CT) in the diagnosis of active arterial extravasation in patients admitted to hospital after blunt abdominal trauma. Four-hundred and ninety-eight consecutive emergent contrast-enhanced computed tomographic images of the abdomen and pelvis were retrospectively reviewed. The presence of and site(s) of active arterial extravasation were recorded. Two radiologists reviewed the images and compared the site(s) of extravasated arterial contrast agent with the site(s) of active hemorrhage established at angiography (n = 9) or surgery (n = 4). Twenty-eight patients' computed tomographic images were identified as showing signs of extravasation of contrast agent representing active arterial bleeding. A total of 49 sources of active arterial extravasation were identified, 37 in 19 patients. A pelvic source of active arterial hemorrhage was most frequent and was typically associated with unstable pelvic fractures (n = 18). Other sources of active arterial hemorrhage included the liver (n = 3), spleen (n = 2), retroperitoneum (n = 1), kidney (n = 1), mesentery (n = 1), abdominal wall (n = 3) and lumbar region (n = 1). Only 9 of 28 patients became sufficiently hemodynamically unstable to warrant angiography. All 9 patients had a pelvic source of arterial extravasation on contrast-enhanced CT, and 7 demonstrated active bleeding requiring embolization. The contrast-enhanced computed tomographic images correctly indicated the anatomical source of bleeding in all 7 cases. In patients who have experienced blunt abdominal trauma, attention should be paid to the computed tomographic features of active arterial hemorrhage. In our series, the pelvis was the most common source of active arterial bleeding, which was typically associated with unstable pelvic fractures.


Genes differentially expressed in responsive and refractory acute leukemia.
DNA microarray in 22 patients with acute leukemia revealed genes which were differentially expressed. Ribosomal protein SA (RPSA), minichromosome maintenance deficient 2 (MCM2) and heterogeneous nuclear ribonucleoprotein A1 (HNRPA1) were significantly upregulated (p<0.05, t test) in refractory patients, suggesting that they may play a role in refractoriness in acute leukemia and could be biomarkers of prognosis.


Variable selection for semiparametric regression models with iterated penalization.
Semiparametric regression models with multiple covariates are commonly encountered. When there are covariates not associated with response variable, variable selection may lead to sparser models, more lucid interpretations and more accurate estimation. In this study, we adopt a sieve approach for the estimation of nonparametric covariate effects in semiparametric regression models. We adopt a two-step iterated penalization approach for variable selection. In the first step, a mixture of the Lasso and group Lasso penalties are employed to conduct the first-round variable selection and obtain the initial estimate. In the second step, a mixture of the weighted Lasso and weighted group Lasso penalties, with weights constructed using the initial estimate, are employed for variable selection. We show that the proposed iterated approach has the variable selection consistency property, even when number of unknown parameters diverges with sample size. Numerical studies, including simulation and analysis of a diabetes dataset, show satisfactory performance of the proposed approach.


Biochemical observations on the protein and nucleic acid metabolism of the rat testis and epididymis after treatment with low doses of alpha-chlorohydrin.
A biochemical study was made on the effects of low doses of alpha-chlorohydrin on the protein and nucleic acid metabolism of the rat testis and epididymis. RNA and protein levels were decreased both in the testis and epididymis. The DNA content of the testis and epididymis did not change after exposure of the animals to the drug. The reduced concentrations of RNA and protein were closely paralleled by the increased activity of proteinase (protein hydrolyzing enzyme) and ribonuclease (RNA degrading enzyme) in the testis and epididymis. The gamma-glutamyl transpeptidase activity of both the testis and epididymis was also reduced indicating the slow transfer of amino acids across the cell membranes of testis and epididymis and thus low protein synthesis. The DNAase levels of rat testis and epididymis did not show any appreciable change in response to the alpha-chlorohydrin treatment. These studies indicate that although there may not be any histological damage in the tissue the metabolic pathways may become defective much earlier before any visible morphological change is discernible.


Salient worries of at-risk youth: needs assessment using the things I worry about scale.
At-risk students in the southern United States were surveyed using the Things I Worry About Scale. From their responses, 13 categories were ranked from most salient to least salient. The rank order obtained in the present study was compared to that obtained with a normative group of youths in Northern Ireland. The two rank orders were found to be significantly correlated. The relatedness of the rank orderings of the two seemingly disparate samples suggests the universality of the Things I Worry About Scale. The merits of using the scale as part of a comprehensive needs assessment are discussed.


Strengthening Brain Research in Africa.
This paper explores the emerging field of neuroscience in Africa, considering the unique genetic diversity, socio-cultural determinants, and health inequalities in the continent. It presents numerous brain research initiatives, such as ABDRN, AMARI, APCDR, and H3Africa, aimed at understanding genetic and environmental factors influencing brain disorders in Africa. Despite numerous challenges like the brain drain phenomenon, inadequate infrastructure, and scarce research expertise, significant progress has been achieved. The paper proposes solutions, including international collaboration, capacity-building efforts, and policies to promote neuroscience research, to enhance the understanding of brain function and address brain-related health issues within the African context.


Effect of the MARA appliance on the position of the lower anteriors in children, adolescents and adults with Class II malocclusion.
Aim of this retrospective study was to investigate the effect of the fixed functional appliance MARA (Mandibular Anterior Repositioning Appliance) on the position of the lower anteriors. For 1.3 years on average, 90 patients with a skeletal and dental Angle Class II malocclusion were treated simultaneously with the MARA and multi-bracket appliances to attain anterior mandibular repositioning. The patients were divided into the following age groups: 36 patients, mean age 10.6 years (children), 28 patients, mean age 14.9 years (adolescents) and 26 patients, mean age 33.7 years (adults). Lateral headfilms were taken at the onset of MARA treatment (T1), upon MARA removal (T2), and one year after MARA removal (T3). IMP angle (IMPA), incisor position with relation to the pogonion perpendicular, ANB angle, overjet and facial type were analyzed using cephalometric software. The degree of crowding was assessed on the study models. The data were subjected to Welch's paired t-test for statistical analysis. In children, an average 0.4 mm mesial shift of the lower incisors (change in proclination +1.7 degrees ) was observed. This movement averaged 1.0 mm in adolescents (change in proclination +3.6 degrees ). The adult age group averaged 1.7 mm (change in proclination +4.5 degrees ). In all age groups, a significant linear correlation was detected between position shift of the lower anteriors and the IMPA angle at T1: strongly protruded lower incisors showed less mesial shift than lingually inclined anteriors. The MARA fixed-functional appliance was an effective device in treating Class II patients in all the age groups studied. The dentoalveolar effect on the lower anteriors was more pronounced in the adult patient group than in the adolescents and children. When the literature on other fixed Class II mechanics is compared, the MARA is revealed as among those with the most Isprinminimal side-effects on the position of the lower anteriors. Ultimately, incisor inclination can be controlled well by therapy with multi-bracket systems.


Isolated myelosarcoma in children--update and review.
Primary myelosarcomas, also called leukemia cutis, granulocytic sarcomas or chloromas, are rare extramedullary manifestations of acute myeloid leukemia (AML) which precede bone marrow involvement. Skin infiltration was the most frequent localization associated with a myelomonocytic differentiation. Although first remission was achieved by most children, risk of relapse seemed to be increased. This might be caused by the specific biology of myelosarcomas, but also may be the result of delayed or reduced treatment. During the AML-BFM-studies 87/93/98 (11/1987-7/2000) 37 children with isolated myelosarcomas were diagnosed. Eighteen of the 37 patients survived with a 5-year overall survival estimation of 0.54+/-0.09 compared to 0.59+/-0.02; p(log rank) = 0.94. However, reduced or delayed treatment in 17 children led to an increased relapse rate of 71% compared to 35% in children treated soon after diagnosis. The 5-year overall survival in these patients was 0.41+/-0.11. According to our experience and review of the literature, an early diagnostic workup is needed in children with unusual skin lesions or tumors, considering myelosarcoma as primary manifestation of AML. Intensive AML-specific chemotherapy is generally recommended soon after diagnosis.


Anti-HIV agents that selectively target retroviral nucleocapsid protein zinc fingers without affecting cellular zinc finger proteins.
Agents that target the two highly conserved Zn fingers of the human immunodeficiency virus (HIV) nucleocapsid p7 (NCp7) protein are under development as antivirals. These agents covalently modify Zn-coordinating cysteine thiolates of the fingers, causing Zn ejection, loss of native protein structure and nucleic acid binding capacity, and disruption of virus replication. Concentrations of three antiviral agents that promoted in vitro Zn ejection from NCp7 and inhibited HIV replication did not impact the functions of cellular Zn finger proteins, including poly(ADP-ribose) polymerase and the Sp1 and GATA-1 transcription factors, nor did the compounds inhibit HeLa nuclear extract mediated transcription. Selectivity of interactions of these agents with NCp7 was supported by molecular modeling analysis which (1) identified a common saddle-shaped nucleophilic region on the surfaces of both NCp7 Zn fingers, (2) indicated a strong correspondence between computationally docked positions for the agents tested and overlap of frontier orbitals within the nucleophilic loci of the NCp7 Zn fingers, and (3) revealed selective steric exclusion of the agents from the core of the GATA-1 Zn finger. Further modeling analysis suggests that the thiolate of Cys49 in the carboxy-terminal finger is the site most susceptible to electrophilic attack. These data provide the first experimental evidence and rationale for antiviral agents that selectively target retroviral nucleocapsid protein Zn fingers.


Circulating hepatocyte growth factor as a diagnostic marker of thrombus formation in patients with cerebral infarction.
Circulating levels of hepatocyte growth factor (HGF) are increased in the early stage of an acute myocardial infarction because of arterial thrombosis. The purpose of this study was to use a new sensitive enzyme-linked immunosorbent assay to investigate whether circulating HGF is increased in patients with cerebral infarction. Circulating HGF was measured in 32 patients with cerebral infarction on admission to hospital and on days 2, 3, 7 and 14 after the onset of symptoms. Serum HGF levels exceeded the mean value +2SD (329pg/ml) measured in controls in 10 of 20 patients (50%) within 6 h after onset and in 15 of 32 patients (47%) within 24 h. Plasma D-dimer was increased in more than half of the patients with elevated HGF values. HGF levels in 16 patients who were measured serially were persistently increased throughout the study period. The results suggests that circulating HGF is a reliable early marker of cerebral infarction, and that this new sensitive HGF assay may be useful for diagnosing cerebral thrombosis.


Adipose-derived stromal vascular fraction (SVF) for the treatment of androgenic alopecia (AGA): a systematic review.
Androgenetic alopecia (AGA) is a common chronic, hereditary, cutaneous and androgen-dependent condition. Low self-esteem and negatively impact quality of life are often consequences of AGA. Clinical treatment of AGA using SVF (Stromal vascular fraction) has been effective. In fact, hair follicle is affected by various environment factors and one of the most important factors is the vascularity of the scalp which is itself affected bySVF. During October 2022 we carried out a systematic review to identify all scientific publications discussing about hair loss treatment with stromal vascular fraction or adipose stem cell. We selected 140 articles. After screening process, we kept 9 articles complying with inclusion criteria. Results: No serious adverse events were reported in all studies. Despite standardized protocol was not found, all studies reported a statistically significant increase in the number (density) of hair after SVF treatment. Two studies found a significant improvement at pull test. An increase of hair diameter was noticed after treatment. The combination between medical therapy and SVF proved to be advantageous. SVF is nowadays at the center of studies in the field of regenerative medicine due to its potential applications in many branches of medicine and surgery. The initial results are very promising but furthermore studies are necessary to establish a methodical and systematic research capable of demonstrating its real benefits and the creation of homogenous treatment protocols.


Intestinal carriage of Clostridium difficile in neonate dogs.
A total of 70 puppies and their dams, distributed in 14 litters, were submitted to weekly fecal examinations for C. difficile during the first 10 weeks after birth. During the study, 94.3% of the puppies and 42.9% of the dams harboured C. difficile at least once in their feces. We calculated that 58% of the puppies carried toxigenic C. difficile at least once during the survey. In the puppies, C. difficile carriage rates ranging from 3.1% to 67.1% were observed at different moments of the observation period. In comparison, C. difficile carriage rate was 1.4% in a control group of healthy dogs more than 3 months old. Discrepancies in the toxigenic phenotype of the C. difficile strains isolated in the same litter showed that the neonate dogs were transiently infected with different strains, and that the dam is often not the source of infection with C. difficile. We could not demonstrate any pathogenicity of C. difficile for neonate dogs.


Establishing radiological percutaneous gastrostomy with balloon-retained tubes as an alternative to endoscopic and surgical gastrostomy in patients with tumours of the head and neck or oesophagus.
The purpose of this study was to report our experience introducing radiological percutaneous gastrostomy (RPG) catheters at a hospital where hitherto only endoscopic and surgical methods have been used. The feasibility, success, time requirements, and complications of RPG were prospectively evaluated during a 12-month period. 26 consecutive patients (median age 63 years, range 41-91 years) underwent gastropexy with T-fasteners followed by insertion of a 12-18 F balloon tube through a peel-away introducer and were followed-up clinically and radiologically. Success and complications occurring within 30 days were assessed. RPG was technically successful in all cases. Median procedure time was 34 min (range 20-90 min), median fluoroscopy time 6.9 min (range 2.3-30 min). 13 surgical gastrostomies were avoided. One minor complication (peristomal leakage) occurred in a patient with gastric reflux and atony. Another patient destroyed the balloon of his tube by injecting food into the balloon port, which led to tube dislocation and peritonitis. In conclusion, radiological gastrostomy can be quickly learned by radiologists and is readily accepted by clinicians. It is an alternative to surgical gastrostomy when percutaneous endoscopic gastrostomy is not feasible, but can also be used as the primary method instead of the endoscopic method.


Brain stem dysfunction related to cervical manipulation. Report of three cases.
Three cases of brain stem dysfunction associated with cervical manipulation are reported. The patients exhibited a spectrum of neurologic deficits, ranging from minimal to severe. Literature concerning the relationship of neck movement and vertebrobasilar blood flow is reviewed and an explanation for the ischemia leading to dysfunction is proposed.


Lipid composition and properties affect protein-mediated carotenoid uptake efficiency from membranes.
Carotenoids are pigments of diverse functions ranging from coloration over light-harvesting to photoprotection. Yet, the number of carotenoid-binding proteins, which mobilize these pigments in physiological media, is limited, and the mechanisms of carotenoid mobilization are still not well understood. The same applies for the determinants of carotenoid uptake from membranes into carotenoproteins, especially regarding the dependence on the chemical properties of membrane lipids. Here, we investigate xanthophyll uptake capacity and kinetics of a paradigmatic carotenoid-binding protein, the homolog of the Orange Carotenoid Protein's C-terminal domain from Anabaena sp. PCC 7120 (AnaCTDH), using liposomes formed from defined lipid species and loaded with canthaxanthin (CAN) and echinenone (ECN), respectively. Phospholipids with different chain length and degree of saturation were investigated. The composition of carotenoid-loaded liposomes directly affected the incorporation yield and storage ratio of CAN and ECN as well as the rate of carotenoid uptake by AnaCTDH. Generally, saturated PC lipids were identified as unsuitable, and a high phase transition temperature of the lipids negatively affected the carotenoid incorporation and storage yield. For efficient carotenoid transfer, the velocity increases with increasing chain length or membrane thickness. An average transfer yield of 93 % and 43 % were obtained for the formation of AnaCTDH(CAN) and AnaCTDH(ECN) holoproteins, respectively. In summary, the most suitable lipids for the formation of AnaCTDH(CAN/ECN) holoproteins by carotenoid transfer from artificial liposomes are phosphatidylcholine (18:1) and phosphatidylglycerol (14:0). Thus, these two lipids provide the best conditions for further investigation of lipid-protein interaction and the carotenoid uptake process.


β-catenin Mutations Are Not Involved in Early-stage Hepatocarcinogenesis Induced by Protoporphyrinogen Oxidase Inhibitors in Mice.
We previously reported the contribution of constitutive androstane receptor (CAR) in cytotoxicity-related hepatocarcinogenesis induced by oxadiazon (OX) or acifluorfen (ACI), two pesticides categorized as protoporphyrinogen oxidase (PROTOX) inhibitors. The molecular characteristics of preneoplastic and neoplastic lesions induced by OX and ACI were immunohistochemically compared to those by phenobarbital (PB), a typical CAR activator, in wild-type (WT) and CAR knockout (CARKO) mice after diethylnitrosamine initiation. We focused on changes in β-catenin and its transcriptional product glutamine synthetase (GS). In PB-promoted foci and adenomas, nuclear accumulation of mutated β-catenin was increased with high frequency. PB treatment also increased the multiplicity and area of GS-positive foci and adenomas in WT mice. No foci and adenomas showed nuclear accumulation of β-catenin and expression of GS in CARKO mice, similar to both genotypes of mice treated with OX and ACI. Interestingly, hepatocellular carcinoma induced in ACI-treated WT mice showed nuclear accumulation of β-catenin and was positive for GS. Our results indicated that β-catenin mutations were not involved in early-stage hepatocarcinogenesis induced by PROTOX inhibitors in mice, although activation of β-catenin and CAR is important in PB-induced tumorigenesis. The significant differences in molecular profiles suggested involvements of multiple mode of actions for hepatocarcinogenesis induced by PROTOX inhibitors.


Erratum: Comparative study of nanostructured carriers of calcium phosphate and magnesium phosphate loaded with SRT1720 for the protection of H2O2-induced senescent endothelium.
[This corrects the article on p. 2068 in vol. 10, PMID: 30093944.].


[Effects of Chemical Fertilizers and Organic Fertilizer on Yield of Ligusticum chuanxiong Rhizome].
To study the effects of different N, P, K and organic fertilizer (OF) on yield of Ligusticum chuanxiong rhizome, in order to provide the theoretical foundation for the establishment of standardization cultivation techniques. The field plot experiments used Ligusticum chuanxiong rhizome which planted in Pengshan as material, and were studied by the four factors and five levels with quadratic regression rotation-orthogonal combination design. According to the data obtained, a function model which could predict the fertilization and yield of Ligusticum chuanxiong rhizome accurately was established. The model analysis showed that the yields of Ligusticum chuanxiong rhizome were significantly influenced by the N, P, K and OF applications. Among these factors, the order of increase rates by the fertilizers was K > OF > N > P; The effect of interaction between N and K, N and OF, K and OF on the yield of Ligusticum chuanxiong rhizome were significantly different. High levels of N and P, N and organic fertilizer, K and organic fertilizer were conducive to improve the yield of Ligusticum chuanxiong rhizome. The results showed that the optimal fertilizer application rates of N was 148.20 - 172.28 kg/hm2, P was 511.92 - 599.40 kg/hm2, K was 249.70 - 282.37 kg/hm2, and OF was 940.00 - 1 104.00 kg/hm2. N, P, K and OF obviously affect the yield of Ligusticum chuanxiong rhizome. K and OF can significantly increase the yield of Ligusticum chuanxiong rhizome. Thus it is suggested that properly high mount of K and OF and appropriate increasing N are two favorable factors for cultivating Ligusticum chuanxiong.


Complementary oligodeoxynucleotide probes of RNA conformation within the Escherichia coli small ribosomal subunit.
The large RNA molecule within each ribosomal subunit is folded in a specific and compact form. The availability of specific 16S RNA sequences on the surface of the small ribosomal subunit has been probed by using complementary oligodeoxynucleotides. The hybridization of 8-15-nucleotide-long oligomers to their RNA complements within the subunit was quantitated by using a nitrocellulose membrane filter binding assay. The probes have been grouped into classes on the basis of sequence-specific binding ability under different conditions of ionic environment, incubation temperature, and subunit activation state [as defined by the ability to bind phenylalanyl-tRNA in response to a poly(uridylic acid) message]. Oligodeoxynucleotides complementary to nucleotides flanking 7-methylguanosine residue 527 and to the 3'-terminal sequence bound 30S subunits regardless of the activation state. Oligodeoxynucleotides that complement 16S ribosomal RNA residues 1-16, 60-70, 685-696, and 1330-1339 and the sequence adjacent to the colicin E3 cleavage site at residue 1502 all bound efficiently only to subunits in an inactivated conformation. Probes complementary to residues 1-11 and 446-455 bound only inactivated subunits, and then with low efficiency. Sequences complementary to nucleotides 6-16, 99-109, 1273-1281, and 1373-1383 bound 30S subunits poorly regardless of the activation state. With one exception, each probe was bound by native or heat-denatured 16S ribosomal RNA (as determined by size-exclusion chromatography). We conclude that complementary oligodeoxynucleotide binding efficiency is a sensitive measure of the availability of specific RNA sequences under easily definable conditions.


Rosemary leaves extract: Anti-snake action against Egyptian Cerastes cerastes venom.
The morbidity caused by viper bites is very dangerous and the anti-venom therapy couldn't treat the local injures such as hemorrhage, edema, necrosis and inflammation of bitten tissues. Searching for safe and effective anti-venom compounds from natural sources is very important. This study was designed to explore the neutralizing ability of Rosmarinus officinalis L. leaves aqueous extract (RMAE) against Egyptian Cerastes cerastes (Cc) viper venom toxicity. The RMAE contained a considerable amount of phenolic and flavonoid contents with 3,300 and 800 mg/100 g dry weight, respectively. The RMAE showed a considerable variation of phenolic acids by using HPLC technique. Rosmarinic acid is the major component of the RMAE which recorded 400 mg/100 g dry weight and 64% of all the identified compounds. In vitro, the RMAE neutralized the enzymatic activities of proteases, l-amino acid oxidases, and phospholipases A2 of the Cc venom dose-dependently. In addition, the RMAE effectively neutralized the gelatinolytic, fibrinogenolytic, hemolytic and procoagulant activities of Cc venom. In vivo, the RMAE markedly reduced lethality, hemorrhage, edema, muscle and liver toxicities induced by Cc venom. In conclusion, the venom neutralizing property of the RMAE gives a new prospect for efficient treatment of the lethal viper bites.


A new genus of cardinalfish from tropical Australia and southern New Guinea (Percomorpha: Apogonidae).
Ozichthys is described as a new monotypic genus, type species Apogon albimaculosus. This species is restricted to tropical Australia and southern New Guinea. The combination of first dorsal fin with VIII visible spines, fused first and second hypurals, epineural on ninth rib, ossified lower preopercle edge, serrated edge of the preopercle, more than three flute canals on post orbit, 23-24 pored lateral- line scales, elongate last lateral-line scale, and sixteen rows of free neuromasts on principal caudal fin-rays will identify this genus from other brownish ground-colored apogonids. This genus is placed in the clade with Apogonichthys, Foa, Fowleria, and Neamia based on color patterns present on the head, body and vertical fins and in having a single pore above and below the raised median canal on each pored lateral-line scale.


Sex-ratio conflicts, kin selection, and the evolution of altruism.
Kin-selection theory has thrived in the explanation of a wide variety of biological phenomena, chiefly the evolution of biological altruism as that found in sterile castes of eusocial insects. Much of the way in which it has been tested is based on the existence of conflicts over sex-ratio production within eusocial colonies. However, despite neatly showing eusocial colonies as arenas where selection at the gene level triggers the appearance of sophisticated disputes, these studies have only demonstrated the existence of genes that act by biasing sex ratios to promote their own spread. Here we argue that such genes depend on the social organization of the colonies where they are expressed, but that they are not, in any way, the precursors of these societies-the major implication being that unequivocal evidence that eusociality evolved through the action of kin-selected altruistic genes is still lacking. Additionally, we highlight the neglect of alternative theories on the explanation of both biological altruism and sex-ratio conflicts, and defend that the enthusiasm with the latter has, in some cases, led to its inappropriate use as a basis for the explanation of other biological characteristics of eusocial organisms, when accounts based on phylogenetic or physiological constraints are also available.


Quantum propensities in the brain cortex and free will.
Capacity of conscious agents to perform genuine choices among future alternatives is a prerequisite for moral responsibility. Determinism that pervades classical physics, however, forbids free will, undermines the foundations of ethics, and precludes meaningful quantification of personal biases. To resolve that impasse, we utilize the characteristic indeterminism of quantum physics and derive a quantitative measure for the amount of free will manifested by the brain cortical network. The interaction between the central nervous system and the surrounding environment is shown to perform a quantum measurement upon the neural constituents, which actualize a single measurement outcome selected from the resulting quantum probability distribution. Inherent biases in the quantum propensities for alternative physical outcomes provide varying amounts of free will, which can be quantified with the expected information gain from learning the actual course of action chosen by the nervous system. For example, neuronal electric spikes evoke deterministic synaptic vesicle release in the synapses of sensory or somatomotor pathways, with no free will manifested. In cortical synapses, however, vesicle release is triggered indeterministically with probability of 0.35 per spike. This grants the brain cortex, with its over 100 trillion synapses, an amount of free will exceeding 96 terabytes per second. Although reliable deterministic transmission of sensory or somatomotor information ensures robust adaptation of animals to their physical environment, unpredictability of behavioral responses initiated by decisions made by the brain cortex is evolutionary advantageous for avoiding predators. Thus, free will may have a survival value and could be optimized through natural selection.


Experience of parents of preschool children in Hawaii during the COVID-19 pandemic.
The COVID-19 pandemic has resulted in major disruption to economic, health, education, and social systems. Families with preschool children experienced extraordinary strain during this time. This paper describes a qualitative study examining the experience of parents of preschool children in Hawaii during the COVID-19 pandemic. Thirteen (N = 13) parents of preschool children living on the island of Oahu, Hawaii, participated in small group discussions occurring in February and March 2021, approximately 1 year after the start of the pandemic in the state. Discussion transcripts were coded and sorted into themes. Four themes emerged: stressors due to the COVID-19 pandemic, family coping and resources, meaning of the COVID-19 crisis to the family, and family adaptation patterns. Themes mapped to the Family Adjustment and Adaptation Response model. Families relied on various resources to cope with stressors experienced due to the COVID-19 pandemic, and adopted new patterns related to seeking healthcare and household emergency preparedness. Findings may inform policies and interventions to support families during the ongoing COVID-19 pandemic and future public health emergencies.


PAS kinase is activated by direct SNF1-dependent phosphorylation and mediates inhibition of TORC1 through the phosphorylation and activation of Pbp1.
We describe the interplay between three sensory protein kinases in yeast: AMP-regulated kinase (AMPK, or SNF1 in yeast), PAS kinase 1 (Psk1 in yeast), and the target of rapamycin complex 1 (TORC1). This signaling cascade occurs through the SNF1-dependent phosphorylation and activation of Psk1, which phosphorylates and activates poly(A)- binding protein binding protein 1 (Pbp1), which then inhibits TORC1 through sequestration at stress granules. The SNF1-dependent phosphorylation of Psk1 appears to be direct, in that Snf1 is necessary and sufficient for Psk1 activation by alternate carbon sources, is required for altered Psk1 protein mobility, is able to phosphorylate Psk1 in vitro, and binds Psk1 via its substrate-targeting subunit Gal83. Evidence for the direct phosphorylation and activation of Pbp1 by Psk1 is also provided by in vitro and in vivo kinase assays, including the reduction of Pbp1 localization at distinct cytoplasmic foci and subsequent rescue of TORC1 inhibition in PAS kinase-deficient yeast. In support of this signaling cascade, Snf1-deficient cells display increased TORC1 activity, whereas cells containing hyperactive Snf1 display a PAS kinase-dependent decrease in TORC1 activity. This interplay between yeast SNF1, Psk1, and TORC1 allows for proper glucose allocation during nutrient depletion, reducing cell growth and proliferation when energy is low.


Depressive symptoms, fruit and vegetables consumption and urinary 3-indoxylsulfate concentration: a nested case-control study in the French Nutrinet-Sante cohort.
Previous epidemiologic studies have provided some evidence of an inverse association between fruit and vegetables consumption and risk of developing recurrent depressive symptoms. This association could possibly be explained by the role of such dietary factors on the gut microbiota. Especially, indole, a metabolite of tryptophan produced by gut bacteria, may be associated with the development of mood disorders. Thus, the purpose of this study was to investigate relationships between fruit and vegetables intake, recurrent depressive symptoms and indole, using measurement of its main urinary excretion form, i.e., 3-indoxylsulfate, as a biomarker. A nested case-control study was conducted in 891 women (aged 45-65) participating to the web-based NutriNet-Santé cohort with available dietary data and biological samples. Cases (individuals with recurrent depressive symptoms, n = 297) were defined as having two Center for Epidemiologic Studies-Depression Scale (CES-D) scores ≥ 16 during the follow-up and were matched with 2 controls having two CES-D scores < 16. Urinary 3-indoxylsulfate concentration was measured as a biomarker of indole production by the gut microbiota. Multivariable conditional logistic regression models were used to test the association of both fruit and vegetables consumption and urine 3-indoxylsulfate measurements with recurrent depressive symptoms. We also tested the association between fruit and vegetables consumption and urinary 3-indoxylsulfate levels using multivariate analysis of variance models. We found a significant inverse association between fruit and vegetables consumption and the risk of having recurrent depressive symptoms over a 2-year period. Fruit and vegetables consumption was inversely associated to urinary 3-indoxylsulfate concentration. However, no significant association was observed between urinary 3-indoxylsulfate levels and recurrent depressive symptoms within this sample. Our results confirm that low fruit and vegetables consumption could be associated with recurrent depressive symptoms. We also found an inverse association between fruit and vegetable intake and urinary levels of 3-indoxylsulfate. However, it is not possible to conclude to a possible mediation role of the indole produced by the gut microbiota from tryptophan, since there was no relationship between 3-indoxylsulfate and recurrent depressive symptoms.


Image presentation in digital radiology: perspectives on the emerging DICOM display function standard and its application.
DICOM (Digital Imaging and Communications in Medicine) Working Group XI, formerly called ACR/NEMA (American College of Radiology/National Electrical Manufacturers' Association) Working Group XI, is currently developing a display function standard. The main objective of the standard is to define mathematically a display function for all image presentation systems. As a secondary objective, the standard aims at providing similarity in gray-scale perception for a given image between display systems of different luminance and at facilitating efficient utilization of the available digital input levels of a display system. The design of the display function incorporates the concept of perceptual linearization. The proposed standard applies to monochrome image presentation devices such as cathode ray tube monitor-display controller systems and digital laser image printers. The standard does not eliminate the use of application-specific display functions but rather ensures their effectiveness. Neither does the standard guarantee equal information transfer between image presentation devices with different physical properties; it does, however, from the basis for applying image processing to compensate for such differences.


Advances on surface structural determination by LEED.
In the last 40 years, low energy electron diffraction (LEED) has proved to be the most reliable quantitative technique for surface structural determination. In this review, recent developments related to the theory that gives support to LEED structural determination are discussed under a critical analysis of the main theoretical approximation-the muffin-tin calculation. The search methodologies aimed at identifying the best matches between theoretical and experimental intensity versus voltage curves are also considered, with the most recent procedures being reviewed in detail.


Social reward processing: A biomarker for predicting psychosis risk?
The desire to obtain social rewards (e.g. positive feedback) features prominently in our lives and relationships, and is relevant to understanding psychopathology - where behavior is often impaired. Investigating social rewards within the psychosis-spectrum offers an especially useful opportunity, given the high rates of impaired social functioning and social isolation. The goal of this study was to investigate hedonic experience associated with social reward processing as a potential biomarker for psychosis risk. This study used a task-based functional magnetic resonance imaging (fMRI) paradigm in adolescents at clinical high-risk for the development of psychosis (CHR, n = 19) and healthy unaffected peers (healthy controls - HC, n = 20). Regional activation and connectivity of the ventromedial prefrontal cortex and ventral striatum were examined in response to receiving positive social feedback relative to an ambiguous feedback condition. Expectations of impaired hedonic processes in CHR youth were generally not supported, as there were no group differences in neural response or task-based connectivity. Although interesting relationships were found linking neural reward response and connectivity with social, anticipatory, and consummatory anhedonia in the CHR group, results are difficult to interpret in light of task limitations. We discuss potential implications for future study designs that seek to investigate social reward processing as a biomarker for psychosis risk.


Cistus incanus from Strandja Mountain as a Source of Bioactive Antioxidants.
The purpose of the present study is to survey the extraction conditions and explore the antioxidant potential of the wild herb Cistus incanus, which is non-traditional in Bulgarian ethnomedicine and widespread in the Strandja Mountain. The influence of the extraction time (0-500 min) and solvent composition (0-50% ethanol in water) on the polyphenols, flavonoid yields and on the antioxidant capacity of the extracts of leaves, stalks (wood parts) and bud mixture were studied. The antioxidant capacity (AOC) was evaluated by use of scavenging assays of 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals. Total polyphenol and flavonoid contents were quantified using UV-vis (ultraviolet-visible) spectrophotometry. The optimal yield of the desired components was obtained with 30% ethanol in water solvent at the 390th min of extraction time. In addition, the influence of seasonality (winter and summer Cistus incanus), and of the different aerial parts-hard-coated seeds, buds, and a mixture of leaves and stalks of the wild plant-on the presence of polyphenols, flavonoids, and AOC were investigated. The present work revealed that the high values of polyphenols, flavonoids and the high AOC occurred not only in the summer leaves, but were also found in the winter leaves, hard-coated seeds, buds, and stalks. Based on the obtained results, the Cistus incanus from Strandja Mountain could be an excellent new source of natural antioxidants in food and for the pharmaceutical industries.


Oxidative and nitrative modifications of enkephalins by reactive nitrogen species.
The interaction of Leucine-enkephalin (Leu-enkephalin) with reactive nitrogen species has been investigated. Reactive nitrogen species are capable of nitrating and oxidizing Leu-enkephalin. HPLC analysis shows the formation of two major enkephalin derivatives by peroxynitrite. The tyrosine amino-terminal residue of Leu-enkephalin is converted either to 3-nitrotyrosine thus producing nitroenkephalin and to dityrosine by dimerization with the production of an enkephalin dimer. The evidence of the formation of the nitroenkephalin and of the enkephalin dimer--dienkephalin--was achieved by electrospray ionisation mass spectrometry. In addition to peroxynitrite, the methylene blue photosensitized oxidation of enkephalin in the presence of nitrite leads to the formation of the nitrated peptide. Moreover, the nitropeptide can be also obtained by peroxidase-generated nitrogen reactive species.


Mechanistic studies on Azospirillum brasilense glutamate synthase.
The reaction mechanism of Azospirillum brasilense glutamate synthase has been investigated by several approaches. 15N nuclear magnetic resonance studies demonstrate that the amide nitrogen of glutamine is reductively transferred to 2-oxoglutarate in an irreversible manner with no release of the transferred ammonia group into the medium. Identical results were obtained using thio-NADPH and acetylpyridine-NADPH, which are shown to be less efficient substrates of the enzyme than NADPH. Similarly, no exchange of the ammonia group being transferred with exogenous ammonium ion was observed during catalysis. The glutamate formed as the product of the iminoglutarate reduction was determined to be in the L configuration. The enzyme was also found to catalyze, under anaerobic conditions, the exchange of the 4proS H of NADPH with solvent both in the absence and in the presence of 2-oxoglutarate and glutamine. The reductive half-reaction is therefore a reversible segment of the overall irreversible amidotransferase reaction. 15N NMR studies also showed that the enzyme does not catalyze glutamate dehydrogenase/oxidase reactions or any observable glutaminase activity under neutral (pH 7.5) conditions. Glutaminase activity was also not observable with the reduced enzyme alone or in the presence of D-glutamate (a competitive inhibitor of glutamate synthase with respect to 2-oxoglutarate, with a Ki of about 11 microM) or with the oxidized enzyme in the presence of 2-oxoglutarate, D-glutamate, or NADP+. These data confirm species-dependent differences of A. brasilense glutamate synthase with respect to the enzyme from other sources.


INITIAL AND PRESENT SITUATION OF FOOD CONTAMINATION IN JAPAN AFTER THE ACCIDENT AT THE FUKUSHIMA DAI-ICHI NUCLEAR POWER PLANT.
The accident at the Fukushima Dai-ichi Nuclear Power Plant (NPP) in March 2011 affected not only the terrestrial environment of Fukushima prefecture and the surrounding area, but also the marine area facing the NPP. Our present study is focused on the concentrations of radionuclides in agricultural products of Fukushima and sea-foods collected off Fukushima after the accident. The regulation value for radiocesium in vegetables, meat and fish was revised from 500 Bq/kg-wet to 100 Bq/kg-wet on 1 April 2012. The overall activity of radiocesium in these products was found to be within the limit of tolerance in respect to Japanese and also international regulations, but there is still radiocesium found at activities greater than this level in edible wild plants, wild mushrooms and game such as boar meat. Although the activities of radionuclides exceeding the regulatory limits were not detected in marine products collected off Fukushima after April 2015, the commercial marine fishery has not received approval in the affected areas except for certain species. We learned from the Fukushima accident that long-term kinetic studies of radionuclides in terrestrial and marine environments is extremely important for prevention of internal contamination, since contamination with radionuclides occurs via the food chain in the environment.


Pollinator effectiveness varies with experimental shifts in flowering time.
The earlier flowering times exhibited by many plant species are a conspicuous sign of climate change. Altered phenologies have caused concern that species could suffer population declines if they flower at times when effective pollinators are unavailable. For two perennial wildflowers, Tradescantia ohiensis and Asclepias incarnata, we used an experimental approach to explore how changing phenology affects the taxonomic composition of the pollinator assemblage and the effectiveness of individual pollinator taxa. After finding in the previous year that fruit set varied with flowering time, we manipulated flowering onset in greenhouses, placed plants in the field over the span of five weeks, and measured pollinator effectiveness as the number of seeds produced after a single visit to a flower. The average effectiveness of pollinators and the expected rates of pollination success were lower for plants of both species flowering earlier than for plants flowering at historical times, suggesting there could be reproductive costs to earlier flowering. Whereas for A. incarnata, differences in average seed set among weeks were due primarily to changes in the composition of the pollinator assemblage, the differences for T. ohiensis were driven by the combined effects of compositional changes and increases over time in the effectiveness of some pollinator taxa. Both species face the possibility of temporal mismatch between the availability of the most effective pollinators and the onset of flowering, and changes in the effectiveness of individual pollinator taxa through time may add an unexpected element to the reproductive consequences of such mismatches.


[Ano-rectal injuries in civilian practice in Cameroon. 10 case reports].
At the Central Hospital of Yaoundé, Cameroon, 10 ano-rectal injuries were treated over a period of 5 years. There were the same number of men and women and all patients were young (range: 7 to 35 years). The cause was illegal abortion in 2 cases and impalement following a fall from a tree in 3. The time lapse between injury and treatment was longer than 24 hours in 5 patients. In 2 cases the lesions were minor and simple debridement was possible. In the remaining 8 cases, construction of a colostomy was required using either the Hartmann terminal-type technique (n = 5) or the exclusion technique (n = 3). Three patients died: one from traumatic shock and two from septic shock. Complications were observed in 4 patients: 2 infections and 2 mechanical complications. Two patients presented permanent sequels including one with partial fecal incontinence. This study confirms the difficulty in management of ano-rectal injuries with limited facilities and reveals the variety of situations that can lead to these injuries especially in children in Africa.


Concordance in goal setting between patients with multiple sclerosis and their rehabilitation team.
To determine the concordance between patients with multiple sclerosis and their clinical team members on the identification of goals for an inpatient rehabilitation stay. Prospective cohort study of patients admitted for rehabilitation in an adult inpatient neurospinal unit at a Rehabilitation Centre in Ottawa, Canada. Twenty-seven patients (11 men and 16 women, mean age of 45.3 yrs) with either a laboratory or a clinically supported diagnosis of multiple sclerosis. Patients rated 55 goals from a preexisting list, indicating the importance of each goal to be addressed during the inpatient stay. The goals fell into five broad domains of health/medical issues, daily activities, mobility, community life, and personal well-being. Patients also identified their five most important individual goals. In a separate session, the clinical team also rated the 55 goals in relation to each patient and identified an independent list of the five most important rehabilitation goals. Main outcome measures included concordance between patient and team ratings in the identification of goals, ratings of the likelihood of success of achieving each goal, and ratings of the amount of change required to realize a minimal clinically important difference. The patients and the team agreed on an average of 1.7 of the patient's five top-rated goals. Compared with the team, patients gave higher importance ratings to goals within the health/medical, mobility, and daily activities domains. They also considered that a greater average improvement would be required to achieve a meaningful benefit, and they gave higher ratings of the likelihood of success in achieving their selected goals. Patients with multiple sclerosis and clinical team members do not necessarily agree on specific goals for a rehabilitation stay. Patients may also have greater expectations than clinicians with respect to the amount of improvement and the likelihood of achieving their goals.


Nafia for the Tigris: The Privy Purse and the infrastructure of development in late Ottoman Iraq, 1882-1914.
Between 1893 and 1908, at least six private consortia and the municipality of Baghdad were denied permission to operate steamships on the Tigris and Euphrates on the grounds that a navigation concession had already been granted to the Privy Purse (hazine-i hassa). The Privy Purse justified its insistence on monopoly with reference to the emerging ideology of development (nafia), though its ideas about the role of steam technology in nafia stood in contrast to those of private investors and other Ottoman bureaucrats. Working from the hazine-i hassa's planning memos and contracts, I show that the private treasury envisioned a primarily agrarian future for Iraq, with steamships serving agricultural aims. As such, it focused on envisioning future steamships rather than managing its existing fleet, while still acquiring dominance over land and transport in the region. However, private companies and officials contested this vision, emphasizing the materiality of existing steamships, their roles in trade, and the potential for commercial competition as a means of resisting British imperial encroachment. After the Committee of Union and Progress came to power in 1908, the Privy Purse was disestablished and its properties reverted to the Finance Ministry, opening a brief window during which steamship companies were encouraged to proliferate. Quickly, however, new comprehensive schemes were proposed, though with railways replacing steamships as the corollary to Iraq's imagined riches. Engaging questions about the futurity of both infrastructure and capital, as well as those posed by the technology-in-use paradigm, this article suggests that the hazine-i hassa is a rich starting point for analysis because the scalar and ontological tensions it embodied highlight how different kinds of futures interact in development planning to affect the present.


Lysosomal degradation of cell organelles. I. Ultrastructural analysis of uptake and digestion of intravenously injected mitochondria by Kupffer cells.
An experimental model comparable to autophagocytosis is presented to evaluate lysosomal degradation of biologic membranes in vivo. This design takes advantage of the efficient phagocytic capacity of Kupffer cells. For this purpose, mitochondria were isolated from one rat liver (inbred strain) and subsequently injected intravenously into a series of rats, which were sacrificed at various time points. The uptake and intralysosomal digestion were examined by electron microscopy. Mitochondria were seen in the sinusoids and attached to the surface of Kupffer cells 1 to 3 minutes after injection. One or two mitochondrial profiles were trapped in cavelike structures often embraced by long hyaloplasmic pseudopods. By 5 and 10 minutes, the mitochondria were in single membrane-bound phagosomes within the Kupffer cells and early signs of mitochondrial alterations were present, e.g., loss of cristae and condensation. At 30 minutes and 1 hour the mitochondria were seen in large vacuoles which contained up to 20 profiles in a single section. The mitochondria showed evident signs of digestion such as membrane fragmentation and flocculent densities. By 4 hours and especially by 8 hours, most digestive vacuoles were laden with flocculent membrane debris. By 24 hours, the Kupffer cells showed multiple lysosomal structures which were irregular in shape and small. These often contained a number of lipid-like droplets of various electron densities and pentalaminar structures. By 2 and 5 days, the Kupffer cells had returned to their normal appearance although the lysosomal apparatus was still prominent. No uptake of mitochondria was seen in endothelial cells, fat-storing cells, or hepatocytes. It is concluded that lysosomes have an efficient capacity to digest mitochondria. Some lipid remnants are not completely or slowly degraded by Kupffer cell lysosomes but remain in "residual bodies" for up to 1 or 2 days.


Late relapse of acute myelogenous leukemia followed by epstein-barr virus-associated lymphoproliferative disease 11 years after allogeneic bone marrow transplantation.
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) following myeloablative conditioning represents the treatment of choice for patients with chemotherapy-resistant leukemia. We describe a 49-year-old man with advanced, refractory acute myelogenous leukemia (AML) that was treated successfully by allogeneic bone marrow transplantation from a sibling donor with HLA mismatched at 1 locus. However, the patient developed a quiescent form of chronic graft-versus-host disease (GVHD) 7 years after transplantation, requiring long-term immunosuppressive therapy. AML relapse was documented 11 years after transplantation. Subsequently, Epstein-Barr virus (EBV)-associated posttransplantation lymphoproliferative disorder (PTLD) was also diagnosed. Immune reconstitution after allo-HSCT might have been impaired by the persistent chronic GVHD and the prolonged administration of immunosuppressive agents. As a result, immune surveillance against remaining quiescent leukemic cells as well as viral infection may have been defective, leading to the relapse of leukemia and EBV-associated PTLD.


Minimally invasive direct coronary artery bypass for the treatment of isolated disease of the left anterior descending coronary artery.
Treatment of isolated stenosis or occlusion of the left anterior descending (LAD) coronary artery through a left anterior mini-thoracotomy has only recently been advocated as an acceptable alternative to standard coronary artery bypass through a sternotomy and with cardiopulmonary bypass grafting. We reviewed our experience with the minimally invasive direct coronary artery bypass (MIDCAB) procedure. A retrospective clinical and angiographic review was conducted on all patients who underwent MIDCAB between October 1998 and February 2002 with subsequent telephone follow-up. Fifty-two consecutive patients (39 men, 13 women, mean [and standard deviation] age 57.3 [12.3] yr) underwent MIDCAB without videoscopic assistance. Eight patients (15%) were converted intraoperatively to sternotomy, and 5 (10%) patients required cardiopulmonary bypass after conversion. There were no perioperative deaths, myocardial infarctions, re-explorations for bleeding or need for transfusions. At a median follow-up time of 27.7 (range 1.9-40.5) months, there were no late deaths or myocardial infarctions. Four patients had anastomotic stenoses and underwent successful percutaneous coronary angioplasty and are asymptomatic. All patients are free of significant anginal symptoms (Canadian Cardiovascular Society class 0 or I). Excellent early and mid-term clinical results can be obtained with MIDCAB. To ensure optimal graft quality, conversion to sternotomy should be liberally employed. It is anticipated that the use of an endoscope may limit this complication.


Evaluating the Effectiveness of an Educational Intervention to Improve the Patient Safety Attitudes of Intern Pharmacists.
Objective. To evaluate the effectiveness of a face-to-face educational intervention in improving the patient safety attitudes of intern pharmacists. Methods. A patient safety education program was delivered to intern pharmacists undertaking The University of Sydney Intern Training Program in 2014. Their patient safety attitudes were evaluated immediately prior to, immediately after, and three-months post-intervention. Underlying attitudinal factors were identified using exploratory factor analysis. Changes in factor scores were examined using analysis of variance. Results. Of the 120 interns enrolled, 95 (78.7%) completed all three surveys. Four underlying attitudinal factors were identified: attitudes towards addressing errors, questioning behaviors, blaming individuals, and reporting errors. Improvements in all attitudinal factors were evident immediately after the intervention. However, only improvements in attitudes towards blaming individuals involved in errors were sustained at three months post-intervention. Conclusion. The educational intervention was associated with short-term improvements in pharmacist interns' patient safety attitudes. However, other factors likely influenced their attitudes in the longer term.


Ferric pyrophosphate citrate: interactions with transferrin.
There are several options available for intravenous application of iron supplements, but they all have a similar structure:-an iron core surrounded by a carbohydrate coating. These nanoparticles require processing by the reticuloendothelial system to release iron, which is subsequently picked up by the iron-binding protein transferrin and distributed throughout the body, with most of the iron supplied to the bone marrow. This process risks exposing cells and tissues to free iron, which is potentially toxic due to its high redox activity. A new parenteral iron formation, ferric pyrophosphate citrate (FPC), has a novel structure that differs from conventional intravenous iron formulations, consisting of an iron atom complexed to one pyrophosphate and two citrate anions. In this study, we show that FPC can directly transfer iron to apo-transferrin. Kinetic analyses reveal that FPC donates iron to apo-transferrin with fast binding kinetics. In addition, the crystal structure of transferrin bound to FPC shows that FPC can donate iron to both iron-binding sites found within the transferrin structure. Examination of the iron-binding sites demonstrates that the iron atoms in both sites are fully encapsulated, forming bonds with amino acid side chains in the protein as well as pyrophosphate and carbonate anions. Taken together, these data demonstrate that, unlike intravenous iron formulations, FPC can directly and rapidly donate iron to transferrin in a manner that does not expose cells and tissues to the damaging effects of free, redox-active iron.


[Association of variants in APPL1 gene with body fat and its distribution in Chinese patients with type 2 diabetic mellitus].
To investigate the impact of single nucleotide polymorphisms (SNPs) in APPL1 gene on body fat and its distribution. 590 unrelated Shanghai residents of Han nationality, including 358 subjects with normal glucose tolerance (NGT) and 232 subjects with type 2 diabetes mellitus (T2DM), underwent measurement of body mass index (BMI), waist circumference (W), hip circumference (H), and femoral circumference (F). Peripheral blood samples were collected to detect the blood sugar, blood lipids, fasting C - peptide (FCP), fasting insulin (FINS), fasting plasma glucose (FGLU), total cholesterol (TC), and triglyceride (TG) 0 and 120 minutes after glucose challenge. Polymerase chain reaction-restriction fragment length polymorphism was used to detect the 2 SNPs (rs3806622 and rs4640525). No differences in the frequencies of rs3806622 and rs4640525 genotypes between the subjects with the BMI < 25 kg/m2 and those with the BMI > or = 25 kg/m2 either in the NGT group or T2DM group. The G allele frequencies of the rs3806622 and rs4640525 genotypes in the T2DM patients with longer W values were significantly higher than those in the patients with shorter W value (OR = 2.26, 95% CI 1.05 - 4.86, and OR = 4.3, 95% CI 1.21 - 14.09). The W values of the T2DM subjects with G alleles were significantly higher than those of the T2DM subjects without G alleles after adjustment of age, sex, and BMI (all P < 0.05). Stepwise regression analysis showed that in addition to sex and BMI, rs4640525 was also an associated factor of waist circumference (all P < 0.05). SNPs (rs3806622 and rs4640525) in APPL1 gene are correlated with body fat distribution in T2DM.


Reliability of kinetic visual field testing in children with mutation-proven retinal dystrophies: Implications for therapeutic clinical trials.
Kinetic visual field testing is used to monitor disease course in retinal dystrophy clinical care and treatment response in treatment trials, which are increasingly recruiting children. This study investigates Goldmann visual field (GVF) changes in young children with mutation-proven retinal dystrophies as they age and with progression of the retinal degeneration. Retrospective review of children ≤ 17 years old with a mutation-proven retinal dystrophy. Objective clinical disease activity was assessed by a retinal degeneration specialist masked to GVF results. Digital quantification of GVF area was performed. Twenty-nine children (58 eyes), ages 5-16, were identified. GVF area increased with age despite progression in 20 children and clinical stability in nine children. Mean ± standard error increase in GVF area/year was 333 ± 130 mm2 (I4e, p = 0.012), 720 ± 155 mm2 (III4e, p < 0.001), and 759 ± 167 mm2 (IV4e, p < 0.001), with greater increases at earlier ages. Repeatability coefficients were 7381 mm2 (I4e), 9379 mm2 (III4e), and 10346 mm2 (IV4e), indicating a large variability. At 2.5 years after the baseline GVF the area increased ≥ 20%, the criterion for positive treatment outcome defined in recent published therapeutic trials, in 38% (I4e), 34% (III4e), and 33% (IV4e) of eyes. In a substantial proportion of children with mutation-proven retinal dystrophies, there is a significant increase in GVF area with age, particularly those < 12 years, despite progression or stability of disease. These findings suggest that change in GVF area in children with retinal dystrophies can be an unreliable measure of response to treatment and on which to base appropriate counseling about visual impairment.


MitoCeption: Transferring Isolated Human MSC Mitochondria to Glioblastoma Stem Cells.
Mitochondria play a central role for cell metabolism, energy production and control of apoptosis. Inadequate mitochondrial function has been found responsible for very diverse diseases, ranging from neurological pathologies to cancer. Interestingly, mitochondria have recently been shown to display the capacity to be transferred between cell types, notably from human mesenchymal stem cells (MSC) to cancer cells in coculture conditions, with metabolic and functional consequences for the mitochondria recipient cells, further enhancing the current interest for the biological properties of these organelles. Evaluating the effects of the transferred MSC mitochondria in the target cells is of primary importance to understand the biological outcome of such cell-cell interactions. The MitoCeption protocol described here allows the transfer of the mitochondria isolated beforehand from the donor cells to the target cells, using MSC mitochondria and glioblastoma stem cells (GSC) as a model system. This protocol has previously been used to transfer mitochondria, isolated from MSCs, to adherent MDA-MB-231 cancer cells. This mitochondria transfer protocol is adapted here for GSCs that present the specific particularity of growing as neurospheres in vitro. The transfer of the isolated mitochondria can be followed by fluorescence-activated cell sorting (FACS) and confocal imaging using mitochondria vital dyes. The use of mitochondria donor and target cells with distinct haplotypes (SNPs) also allows detection of the transferred mitochondria based on the concentration of their circular mitochondrial DNA (mtDNA) in the target cells. Once the protocol has been validated with these criteria, the cells harboring the transferred mitochondria can be further analyzed to determine the effects of the exogenous mitochondria on biological properties such as cell metabolism, plasticity, proliferation and response to therapy.