Genetic analysis of Mint/X11 proteins: essential presynaptic functions of a neuronal adaptor protein family.
Mints/X11s are adaptor proteins composed of three isoforms: neuron-specific Mints 1 and 2, and the ubiquitously expressed Mint 3. We have now analyzed constitutive and conditional knock-out mice for all three Mints/X11s. We found that approximately 80% of mice lacking both neuron-specific Mint isoforms (Mints 1 and 2) die at birth, whereas mice lacking any other combination of Mint isoforms survive normally. The approximately 20% surviving Mint 1/2 double knock-out mice exhibit a decrease in weight and deficits in motor behaviors. Hippocampal slice electrophysiology uncovered a decline in spontaneous neurotransmitter release, lowered synaptic strength, and enhanced paired-pulse facilitation in Mint-deficient mice, suggesting a decreased presynaptic release probability. Acute ablation of Mint expression in cultured neurons from conditional Mint 1/2/3 triple knock-in mice also revealed a decline in spontaneous release, confirming that deletion of Mints impair presynaptic function. Quantitation of synaptic proteins showed that acute deletion of Mints caused a selective increase in Munc18-1 and Fe65 proteins, and overexpression of Munc18-1 in wild-type neurons also produced a decrease in spontaneous release, suggesting that the interaction of Mints with Munc18-1 may contribute to the presynaptic phenotype observed in Mint-deficient mice. Our studies thus indicate that Mints are important regulators of presynaptic neurotransmitter release that are essential for mouse survival.


Referral to a new psychological therapy service is associated with reduced utilisation of healthcare and sickness absence by people with common mental health problems: a before and after comparison.
Improving Access to Psychological Therapies (IAPT) is a new programme designed to reduce disease burden to the individual and economic burden to the society of common mental health problems (CMHP). This is the first study to look at the impact of IAPT on health service utilisation and sickness absence using routine data. The authors used pseudonymised secure and privately linked (SAPREL) routinely collected primary, secondary care and clinic computer data from two pilot localities. The authors explored antidepressant prescribing, accident and emergency and outpatients attendances, inpatient stays, bed days, and sick certification. The authors compared the registered population with those with CMHP. The authors then made a 6 months before and after comparison of people referred to IAPT with age-sex and practice-matched controls. People with CMHP used more health resources than those without CMHP: more prescriptions of antidepressants 5.25 (95% CI 5.38 to 5.13), inpatient episodes 4.89 (95% CI 5.0 to 4.79), occupied bed days 1.25 (95% CI 0.95 to 1.55), outpatient 1.5 (95% CI 1.40 to 1.63) and emergency department attendances 0.34 (95% CI 0.31 to 0.37), and medical certificates 0.29 (95% CI 0.26 to 0.32). Comparison of service utilisation 6 months before and after referral to IAPT was associated with reduced use of emergency department attendances (mean difference: 0.12 (95% CI 0.06 to 0.19, p<0.001)). However, the number of prescriptions of antidepressants increased mean difference -0.15 (95% CI 0.02-0.29, p=0.028). People with CMHP use more healthcare resources. Referral to the IAPT programme is associated with a subsequent reduction in emergency department attendances, sickness certification and improved adherence to drug treatment.


A prospective cohort study of body size and risk of head and neck cancers in the NIH-AARP diet and health study.
The association between body size and head and neck cancers (HNCA) is unclear, partly because of the biases in case-control studies. In the prospective NIH-AARP cohort study, 218,854 participants (132,288 men and 86,566 women), aged 50 to 71 years, were cancer free at baseline (1995 and 1996), and had valid anthropometric data. Cox proportional hazards regression was used to examine the associations between body size and HNCA, adjusted for current and past smoking habits, alcohol intake, education, race, and fruit and vegetable consumption, and reported as HR and 95% confidence intervals (CI). Until December 31, 2006, 779 incident HNCAs occurred: 342 in the oral cavity, 120 in the oro- and hypopharynx, 265 in the larynx, 12 in the nasopharynx, and 40 at overlapping sites. There was an inverse association between HNCA and body mass index, which was almost exclusively among current smokers (HR = 0.76 per each 5 U increase; 95% CI, 0.63-0.93), and diminished as initial years of follow-up were excluded. We observed a direct association with waist-to-hip ratio (HR = 1.16 per 0.1 U increase; 95% CI, 1.03-1.31), particularly for cancers of the oral cavity (HR, 1.40; 95% CI, 1.17-1.67). Height was also directly associated with total HNCAs (P = 0.02), and oro- and hypopharyngeal cancers (P < 0.01). The risk of HNCAs was associated inversely with leanness among current smokers, and directly with abdominal obesity and height. Our study provides evidence that the association between leanness and risk of HNCAs may be due to effect modification by smoking.


A case of probable codeine poisoning in a young infant after the use of a proprietary cough and cold medicine.
We report a case of probable poisoning with codeine phosphate in a 3-month-old infant, which was associated with excessive dosing and concomitant use of antihistamines. Investigation into the patient's drug history identified the recent use of a proprietary cough and cold medicine containing codeine phosphate and dexchlorpheniramine. The prescribing information, available from a popular prescribing handbook, listed only one dosage for children, without any adjustment for age or size, and did not bear any warning for its use in young children. A review of the handbook identified seven additional remedies that were similarly listed. Medical practitioners and pharmacists should be aware of this prescribing pitfall. Improvements are needed in the prescribing information pertaining to the use of cough and cold formulas containing opioid or opioid-like antitussives among young children, and clear warnings should be included in drug inserts and formularies.


Fiber and magnesium intake and incidence of type 2 diabetes: a prospective study and meta-analysis.
Prospective studies on fiber and magnesium intake and risk of type 2 diabetes mellitus were inconsistent. We examined associations between fiber and magnesium intake and risk of type 2 diabetes and summarized existing prospective studies by meta-analysis. We conducted a prospective cohort study of 9702 men and 15 365 women aged 35 to 65 years who were observed for incident diabetes from 1994 to 2005. Dietary intake of fiber and magnesium were measured with a validated food-frequency questionnaire. We estimated the relative risk (RR) by means of Cox proportional hazards analysis. We searched PubMed through May 2006 for prospective cohort studies of fiber and magnesium intake and risk of type 2 diabetes. We identified 9 cohort studies of fiber and 8 studies of magnesium intake and calculated summary RRs by means of a random-effects model. During 176 117 person-years of follow-up, we observed 844 incident cases of type 2 diabetes in the European Prospective Investigation Into Cancer and Nutrition-Potsdam. Higher cereal fiber intake was inversely associated with diabetes risk (RR for extreme quintiles, 0.72 [95% confidence interval [CI], 0.56-0.93]), while fruit fiber (0.89 [95% CI, 0.70-1.13]) and vegetable fiber (0.93 [95% CI, 0.74-1.17]) were not significantly associated. Meta-analyses showed a reduced diabetes risk with higher cereal fiber intake (RR for extreme categories, 0.67 [95% CI, 0.62-0.72]), but no significant associations for fruit (0.96 [95% CI, 0.88-1.04]) and vegetable fiber (1.04 [95% CI, 0.94-1.15]). Magnesium intake was not related to diabetes risk in the European Prospective Investigation Into Cancer and Nutrition-Potsdam (RR for extreme quintiles, 0.99 [95% CI, 0.78-1.26]); however, meta-analysis showed a significant inverse association (RR for extreme categories, 0.77 [95% CI, 0.72-0.84]). Higher cereal fiber and magnesium intakes may decrease diabetes risk.


Identification of hot spots of malaria transmission for targeted malaria control.
Variation in the risk of malaria within populations is a frequently described but poorly understood phenomenon. This heterogeneity creates opportunities for targeted interventions but only if hot spots of malaria transmission can be easily identified. We determined spatial patterns in malaria transmission in a district in northeastern Tanzania, using malaria incidence data from a cohort study involving infants and household-level mosquito sampling data. The parasite prevalence rates and age-specific seroconversion rates (SCRs) of antibodies against Plasmodium falciparum antigens were determined in samples obtained from people attending health care facilities. Five clusters of higher malaria incidence were detected and interpreted as hot spots of transmission. These hot spots partially overlapped with clusters of higher mosquito exposure but could not be satisfactorily predicted by a probability model based on environmental factors. Small-scale local variation in malaria exposure was detected by parasite prevalence rates and SCR estimates for samples of health care facility attendees. SCR estimates were strongly associated with local malaria incidence rates and predicted hot spots of malaria transmission with 95% sensitivity and 85% specificity. Serological markers were able to detect spatial variation in malaria transmission at the microepidemiological level, and they have the potential to form an effective method for spatial targeting of malaria control efforts.


Risk and protective factors for mental disorders with onset in childhood/adolescence: An umbrella review of published meta-analyses of observational longitudinal studies.
The patho-etiology of mental disorders with onset in childhood or adolescence remains largely unknown. We conducted an umbrella review of meta-analyses (MAs) on environmental factors associated with mental disorders with onset in childhood/adolescence. We searched Pubmed-MEDLINE/EMBASE/PsycInfo databases, last search April 29th, 2020. Quality of MAs was measured with AMSTAR-2. Out of 6851 initial references, ten articles met inclusion criteria, providing 23 associations between 12 potential environmental factors and nine disorders (cases: 8884; N = 3,660,670). While almost half of the associations were nominally significant, none of them met criteria from either convincing or highly suggestive evidence. A single association was supported by suggestive evidence (maternal exposure to lithium or antipsychotics with neuromotor deficits), but it was affected by confounding by indication. Ten more associations had weak evidence, and 12 associations were not statistically significant. Quality of meta-analyses was rated as high in two, moderate in one, low in four, critically low in two, and not pertinent in one (individual participant data). Methodologically-sound research is needed in this field.


The use of dry needling for a subject with acute onset of neck pain: a case report.
Neck pain is a common complaint treated by the physical therapist. Trigger points (TrPs) have been studied as a source of neuromusculoskeletal pain, though the ability of clinicians to accurately locate a TrP is not well supported. Dry needling (DN) is an intervention utilized by physical therapists where a monofilament needle is inserted into soft tissue in order to reduce pain thereby facilitating return to prior level of function. The purpose of this case report is to report the outcomes of DN as a primary treatment intervention for acute, non-specific cervical region pain. The subject was an active 64-year-old female who self- referred for cervical pain following lifting heavy boxes while moving into a new home. She had a history of multi-level cervical fusion and recurrent cervical pain that physical therapy helped to control over the past few years. Physical examination supported a diagnosis of acute cervical region strain. Objective findings included decreased cervical active range of motion (AROM) and upper extremity strength, as well as, reproduction of pain symptoms upon palpation indicating the likelihood of TrPs in the right upper trapezius, levator scapula, supraspinatus, and infraspinatus musculature. She was treated using DN to the aforementioned muscles for two sessions, and no other interventions were performed in order to determine the effectiveness of DN as a primary intervention strategy without other interventions masking the effects of DN. Clinically meaningful improvements were noted in pain and disability, as measured by the Neck Disability Index and Quadruple Visual Analog Scale. Physical examination denoted minimal to no change in cervical AROM (likely associated with multi-level fusion), except for right lateral flexion, and no change in shoulder flexion/ abduction MMT. The patient was able to return to daily and work activities without further functional limitations caused by pain. This case report shows promising outcomes for the use of DN in the treatment of non-specific cervical region strain. Further research is recommended to determine if DN is clinically beneficial independent of other therapeutic interventions/ postural corrections such as general or specific exercises targeting the affected musculature, or other "manual" therapy techniques such as manipulation or non-thrust mobilization. Level 4.


Antioxidant activity of gamma-oryzanol: mechanism of action and its effect on oxidative stability of pharmaceutical oils.
Gamma-oryzanol, a phytosteryl ferulate mixture extracted from rice bran oil, has a wide spectrum of biological activities; in particular, it has antioxidant properties and is often used in cosmetic formulations as a sunscreen. The first objective of the present investigation was to elucidate the molecular mechanism(s) of the antioxidant activity of gamma-oryzanol by utilising different in vitro model systems, such as scavenging of stable DPPH radical, OH and O2- radicals scavenging, and azocompound AMVN-initiated lipid peroxidation. The effect of gamma-oryzanol on the oxidative stability of vegetable oils of pharmaceutical and cosmetic interest was then evaluated in a oxidation accelerate test and compared with the effect of the well-known antioxidants BHA and BHT. Our results demonstrate that gamma-oryzanol is an organic radical scavenger able to prevent AMVN-triggered lipoperoxidation. Moreover, when added to oils at concentrations ranging between 2.5 and 10 mmol/kg, gamma-oryzanol shows a dose-dependent increase of the induction times; in particular, it improved the oxidative stability of oils very prone to lipoperoxidation because of their high content of polyunsaturated fatty acids. On the ground of our results, we can conclude that gamma-oryzanol may have a potential application for the stabilization of lipidic raw materials.


Ultrasound diagnosis of uterine myomas and complications in pregnancy.
To evaluate myomas for ultrasound-documented size, location, position, and relation to the placenta, and to relate these findings to complications during pregnancy, at delivery, and in the puerperium. Among 12,708 pregnant patients who had ultrasound scans, 492 had uterine myomas. Single myomas were found in 88% of cases and multiple myomas in 12%. The myomas were evaluated for size, number, position, location, relationship to the placenta, and echogenic structure, and the outcome of pregnancy was compared to that of patients in the control group. A statistically significant increased incidence of threatened abortion, threatened preterm delivery, abruptio placentae, and pelvic pain was observed in patients with uterine myomas (P < .001). Abruptio placentae was particularly evident in women with myoma volumes greater than 200 cm3, submucosal location, or superimposition of the placenta. Pelvic pain was related to myoma volume greater than 200 cm3 and ultrasound findings of heterogeneous echo patterns and cystic areas. Mode of delivery, abortion, preterm birth, premature rupture of membranes, and fetal growth did not seem to be affected by the presence of myomas. Thirty-two women with uterine myomas were managed surgically. Thirteen underwent myomectomy during pregnancy. Of these, eight delivered at term and five delivered preterm after the 32nd week of gestation. None of the deliveries were associated with neonatal death. The other 19 patients had surgery at delivery. Nine myomectomies were performed at cesarean delivery. Of these, three were complicated by severe hemorrhage necessitating hysterectomy. Another nine hysterectomies were performed during cesarean and one after vaginal delivery. In addition to myoma size, the ultrasound evaluation of pregnant women with myomas should include position, location, relationship to the placenta, and echogenic structure. These ultrasound findings make it possible to identify women at risk for myoma-related complications and could be useful in managing the pregnancy.


Metabolic effects of fructose and the worldwide increase in obesity.
While virtually absent in our diet a few hundred years ago, fructose has now become a major constituent of our modern diet. Our main sources of fructose are sucrose from beet or cane, high fructose corn syrup, fruits, and honey. Fructose has the same chemical formula as glucose (C(6)H(12)O(6)), but its metabolism differs markedly from that of glucose due to its almost complete hepatic extraction and rapid hepatic conversion into glucose, glycogen, lactate, and fat. Fructose was initially thought to be advisable for patients with diabetes due to its low glycemic index. However, chronically high consumption of fructose in rodents leads to hepatic and extrahepatic insulin resistance, obesity, type 2 diabetes mellitus, and high blood pressure. The evidence is less compelling in humans, but high fructose intake has indeed been shown to cause dyslipidemia and to impair hepatic insulin sensitivity. Hepatic de novo lipogenesis and lipotoxicity, oxidative stress, and hyperuricemia have all been proposed as mechanisms responsible for these adverse metabolic effects of fructose. Although there is compelling evidence that very high fructose intake can have deleterious metabolic effects in humans as in rodents, the role of fructose in the development of the current epidemic of metabolic disorders remains controversial. Epidemiological studies show growing evidence that consumption of sweetened beverages (containing either sucrose or a mixture of glucose and fructose) is associated with a high energy intake, increased body weight, and the occurrence of metabolic and cardiovascular disorders. There is, however, no unequivocal evidence that fructose intake at moderate doses is directly related with adverse metabolic effects. There has also been much concern that consumption of free fructose, as provided in high fructose corn syrup, may cause more adverse effects than consumption of fructose consumed with sucrose. There is, however, no direct evidence for more serious metabolic consequences of high fructose corn syrup versus sucrose consumption.


WITHDRAWN: Application of Chemotherapeutic Drugs and Convectionenhanced Delivery Technology in Glioma
Since the authors are not responding to the editor's requests to fulfill the editorial requirement, therefore, the article has been withdrawn from the website of the journal Anti-Cancer Agents in Medicinal Chemistry. Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused. The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorialpolicies-main.php. It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript, the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.


Cyclosporin A Administration During Ex Vivo Lung Perfusion Preserves Lung Grafts in Rat Transplant Model.
Despite the benefits of ex vivo lung perfusion (EVLP) such as lung reconditioning, preservation, and evaluation before transplantation, deleterious effects, including activation of proinflammatory cascades and alteration of metabolic profiles have been reported. Although patient outcomes have been favorable, further studies addressing optimal conditions are warranted. In this study, we investigated the role of the immunosuppressant drug cyclosporine A (CyA) in preserving mitochondrial function and subsequently preventing proinflammatory changes in lung grafts during EVLP. Using rat heart-lung blocks after 1-hour cold preservation, an acellular normothermic EVLP system was established for 4 hours. CyA was added into perfusate at a final concentration of 1 μM. The evaluation included lung graft function, lung compliance, and pulmonary vascular resistance as well as biochemical marker measurement in the perfusate at multiple time points. After EVLP, single orthotopic lung transplantation was performed, and the grafts were assessed 2 hours after reperfusion. Lung grafts on EVLP with CyA exhibited significantly better functional and physiological parameters as compared with those without CyA treatment. CyA administration attenuated proinflammatory changes and prohibited glucose consumption during EVLP through mitigating mitochondrial dysfunction in lung grafts. CyA-preconditioned lungs showed better posttransplant lung early graft function and less inflammatory events compared with control. During EVLP, CyA administration can have a preconditioning effect through both its anti-inflammatory and mitochondrial protective properties, leading to improved lung graft preservation, which may result in enhanced graft quality after transplantation.


An IAP in action: the multiple roles of survivin in differentiation, immunity and malignancy.
The proteolytic activity of caspases is tightly controlled by the inhibitor of apoptosis protein (IAP) family that has evolved to protect cells from unwanted self-execution by fortuitous activation of the death cascade. Survivin is a 17 kD protein that contains only a single BIR and no RING domain. It stands out for its close association with cancer where its expression correlates with drug resistance and poor prognosis. In the nucleus, survivin binds to microtubules and assists in chromosomal segregation and cytokinesis during mitosis. In the cytoplasm, survivin inhibits apoptosis by interacting with caspase-9 in the presence of the HBXIP cofactor, by binding to Smac or associating with XIAP. Recent data demonstrate that survivin is also expressed in normal proliferating hematopoietic cells as well as in terminally differentiated neutrophils, where it, following upregulation by hematopoietic growth factors, inhibits apoptosis independent of the cell cycle.


Impact of working memory load on FMRI resting state pattern in subsequent resting phases.
The default-mode network (DMN) is a functional network with increasing relevance for psychiatric research, characterized by increased activation at rest and decreased activation during task performance. The degree of DMN deactivation during a cognitively demanding task depends on its difficulty. However, the relation of hemodynamic responses in the resting phase after a preceding cognitive challenge remains relatively unexplored. We test the hypothesis that the degree of activation of the DMN following cognitive challenge is influenced by the cognitive load of a preceding working-memory task. Twenty-five healthy subjects were investigated with functional MRI at 3 Tesla while performing a working-memory task with embedded short resting phases. Data were decomposed into statistically independent spatio-temporal components using Tensor Independent Component Analysis (TICA). The DMN was selected using a template-matching procedure. The spatial map contained rest-related activations in the medial frontal cortex, ventral anterior and posterior cingulate cortex. The time course of the DMN revealed increased activation at rest after 1-back and 2-back blocks compared to the activation after a 0-back block. We present evidence that a cognitively challenging working-memory task is followed by greater activation of the DMN than a simple letter-matching task. This might be interpreted as a functional correlate of self-evaluation and reflection of the preceding task or as relocation of cerebral resources representing recovery from high cognitive demands. This finding is highly relevant for neuroimaging studies which include resting phases in cognitive tasks as stable baseline conditions. Further studies investigating the DMN should take possible interactions of tasks and subsequent resting phases into account.


Clinical significance of growth differentiation factor 11 in colorectal cancer.
Growth differentiation factor 11 (GDF11), a member of the transforming growth factor-beta superfamily and bone morphogenetic protein (BMP) subfamily, plays a role in regulation of development and differentiation. Although some members of BMP subfamily have been reported to correlate with cancer, the significance of GDF11 has not been studied in a clinical oncology setting. The current study explored the clinicopathological significance of GDF11 expression in colorectal cancer. Quantitative real-time reverse transcription-PCR in colorectal cancer specimens obtained from 130 patients showed that GDF11 mRNA expression in cancer tissue was significantly higher than in normal tissue (p=0.001). Tumors were classified as high GDF11 expression (n=65) or low GDF11 expression (n=65). Patients whose tumors had high GDF11 expression showed a high frequency of lymph node metastasis (p=0.049) and had more cancer-related deaths (p=0.040). Furthermore, the patients with high GDF11 expression had significantly poorer overall survival than those with low expression (p=0.0334). Although multivariate analysis showed that GDF11 was not an independent prognostic factor, these findings suggest that GDF11 may be a novel diagnostic and prognostic biomarker in patients with colorectal cancer.


Hemolysis during membrane plasma separation with pulsed flow filtration enhancement.
The use of pulsed blood flow in membrane plasmapheresis permits enhancement of plasma filtration yet may result in high levels of hemolysis due to large increases in instantaneous transmembrane pressure (TMP). This work investigates the occurrence of hemolysis as a function of TMP and wall shear rates (gamma w) for both steady and pulsed blood flow conditions. Two types of hollow fiber filters with identical polypropylene membranes but different lengths and membrane areas (0.1 and 0.25 m2) were tested. Fresh citrated bovine blood was circulated through the fibers at various blood flowrates and TMP in a single pass circuit using a pulsation generator, made of a single roller peristaltic pump. The free hemoglobin concentration of the plasma, Hbm, was measured from permeate samples collected at each set of TMP and gamma w conditions. It was found that the net hemolysis generated by the filtration was proportional to the membrane area. This justified the introduction of an hemolysis index, IH, equal to the plasma hemoglobin per unit membrane area. The boundary for the occurrence of hemolysis was thus defined by setting IH = 30 mg/dl.m2. For both steady and pulsed flow conditions the hemolysis boundaries were found to be straight lines in the TMP-gamma w plane. They were identical for the two filters under steady flow but different for pulsed flow. At the same time mean wall shear rates hemolysis occurred at a lower time mean TMP under pulsed flow conditions than under steady flow conditions.


Critical stages of extracting DNA from Aspergillus fumigatus in whole-blood specimens.
A standardized protocol for extracting DNA from Aspergillus fumigatus has been proposed by the European Aspergillus PCR Initiative (EAPCRI). Using meta-regression analysis, the EAPCRI showed certain stages of the process to be critical to providing a satisfactory analytical sensitivity. The study investigated each step of the EAPCRI protocol by elimination and monitored the influence on Aspergillus PCR performance.


Intracardiac ECHO Integration with Three Dimensional Mapping: Role in AF Ablation.
Background: Catheter ablation of atrial fibrillation (AF) is typically guided by 3D mapping. This involves point-by-point reconstruction of the 3D virtual anatomy and may be time consuming and require substantial fluoroscopy exposure. Intracardiac echocardiography (ICE) affords real time imaging of the cardiac structures during mapping and ablation. Methods: Between February and May 2007, 15 patients (100% men, 10 with paroxysmal AF) presenting for AF ablation were offered mapping using a novel system integrating 3D mapping and ICE. A modified ICE probe with a location sensor tracked by the mapping system was positioned in the right atrium (RA). This allowed acquisition of ECG gated images of the left atrium (LA). Endocardial contours were traced on each image and were used to generate a registered 3D map. Results: 3D maps took a mean of 51+/-25 minutes to create, PRIOR to entering the LA and without fluoroscopy. Pulmonary veins and the esophagus were rendered in 3D. A complete map was built from a mean of 46+/-19 contours. Upon instrumentation of the left atrium, the maps were easily distorted if points collected by the mapping catheter were combined with the original map, due to deformation of the left atrial geometry by the relatively stiff ablation catheter. Pulmonary vein antrum isolation was guided by a circular mapping catheter. Since this catheter could not be visualized on the CARTO map, fluoroscopy was used to track its position and the contact between the ablation catheter and the circular mapping catheter. No substantial reduction in fluoroscopy time was thus realized, as expected. At 10+/-1 months of followup, 73% of the patients were in sinus rhythm after the initial three month blanking period. No patient suffered any complications related to the procedure or in follow-up. Conclusions: A mapping system combining ICE and 3D electroanatomical mapping can feasibly reconstruct a 3D shell of the LA and the pulmonary veins without the need to enter the left heart. The map created is sensitive to distortion during point-by-point mapping with the standard ablation catheter.


Population-based drug-related anaphylaxis in children and adolescents captured by South Carolina Emergency Room Hospital Discharge Database (SCERHDD) (2000-2002).
Anaphylaxis is a life-threatening condition; drug-related anaphylaxis represents approximately 10% of all cases. We assessed the utility of a statewide emergency department (ED) database for identifying drug-related anaphylaxis in children by developing and validating an algorithm composed of ICD-9-CM codes. There were 1 314,760 visits to South Carolina (SC) emergency departments (EDs) for patients <19 years in 2000-2002. We used ICD-9-CM disease or external cause of injury codes (E-codes) that suggested drug-related anaphylaxis or a severe drug-related allergic reaction. We found 50 cases classifiable as probable or possible drug-related anaphylaxis and 13 as drug-related allergic reactions. We used clinical evaluation by two pediatricians as the 'alloyed gold standard'1 for estimating sensitivity, specificity, and positive predictive value (PPV) of our algorithm. ED-treated drug-related anaphylaxis in the SC pediatric population was 1.56/100,000 person-years based on the algorithm and 0.50/100,000 person-years based on clinical evaluation. Assuming the disease codes we used identified all potential anaphylaxis cases in the database, the sensitivity was 1.00 (95%CI: 0.79, 1.00), specificity was 0.28 (95%CI: 0.16, 0.43), and the PPV was 0.32 (0.20, 0.47) for the algorithm. Sensitivity analyses improved the measurement properties of the algorithm. E-codes were invaluable for developing an anaphylaxis algorithm although the frequently used code of E947.9 was often incorrectly applied. We believe that our algorithm may have over-ascertained drug-related anaphylaxis patients seen in an ED, but the clinical evaluation may have under-represented this diagnosis due to limited information on the offending agent in the abstracted ED records. Post-marketing drug surveillance using ED records may be viable if clinicians were to document drug-related anaphylaxis in the charts so that billing codes could be assigned properly.


The T197A Knock-in Model of Cdkn1b Gene to Study the Effects of p27 Restoration In Vivo.
The CDK inhibitor, p27kip1, encoded by the Cdkn1b gene can negatively modulate cell proliferation. The control of p27 activity during the cell cycle is regulated at multiple levels, including transcription, translation, and protein stability. The last residue of p27 (threonine 198 in human, threonine 197 in mouse) is involved in the control of protein stability. We have generated a murine knock-in model (Cdkn1b T197A) in which threonine 197 is replaced by alanine, which renders p27 protein highly unstable due to a high rate of proteasomal degradation. Expectedly, Cdkn1b T197A/T197A mice present with increased body size and weight, organomegaly, and multiple organ hyperplasia, similar to what is observed in Cdkn1b KO/KO mice. We investigated the effects exerted by the restoration of normal levels of p27 protein in the tissue of Cdkn1b T197A/T197A mice. We found that proteasome inhibition with bortezomib rescues the hyperplasia induced by the lack of p27 expression in Cdkn1b T197A/T197A but not in Cdkn1b KO/KO mice. However, BAY 11-7082, a proteasome inhibitor that stabilizes IκB but not p27, fails to rescue hyperplasia in Cdkn1b T197A/T197A mice. Bortezomib increases p27 half-life and reduces the proliferation in MEFs derived from Cdkn1b T197A/T197A but not from Cdkn1b WT/WT mice, whereas BAY 11-7082 had no effect on the protein levels of p27 and on the proliferation rate of Cdkn1b T197A/T197A MEFs.The results presented here demonstrate that Cdkn1b T197A/T197A mice represent an attractive in vivo model to investigate whether the targeting of p27 degradation machinery might prove beneficial in the treatment of a variety of human proliferative disorders caused by increased turnover of p27 protein.


Molecular comparisons of freshwater and marine isolates of the same morphospecies of heterotrophic flagellates.
Heterotrophic flagellates are key components of all ecosystems. Understanding the patterns of biodiversity of these organisms is thus particularly important. Here we analyzed the intraspecific diversity of 10 morphospecies of heterotrophic flagellates comprising representatives of the Apusozoa (2 morphospecies) and Kinetoplastea (8 morphospecies), all belonging to the most common flagellates with worldwide distribution. Most morphospecies showed a mixing of lineages isolated from diverse habitats, indicating that some lineages of these morphospecies had been able to colonize different habitats several times. Furthermore, our results revealed remarkable levels of genetic divergence within most of the morphospecies studied, underlining the difficulty of correctly determining species by means of morphology alone. Many cryptic or pseudocryptic species seem to occur. Our results revealed clear divergence between marine and freshwater lineages of the morphospecies Ancyromonas sigmoides, showing that freshwater lineages have not been able to colonize marine environments and marine lineages have not been able to colonize freshwater environments for a long time.


Adult Patients With Bronchiectasis: A First Look at the US Bronchiectasis Research Registry.
We sought to describe the characteristics of adult patients with bronchiectasis enrolled in the US Bronchiectasis Research Registry (BRR). The BRR is a database of patients with non-cystic-fibrosis bronchiectasis (NCFB) enrolled at 13 sites in the United States. Baseline demographic, spirometric, imaging, microbiological, and therapeutic data were entered into a central Internet-based database. Patients were subsequently analyzed by the presence of NTM. We enrolled 1,826 patients between 2008 and 2014. Patients were predominantly women (79%), white (89%), and never smokers (60%), with a mean age of 64 ± 14 years. Sixty-three percent of the patients had a history of NTM disease or NTM isolated at baseline evaluation for entry into the BRR. Patients with NTM were older, predominantly women, and had bronchiectasis diagnosed at a later age than those without NTM. Gastroesophageal reflux disease (GERD) was more common in those with NTM, whereas asthma, primary immunodeficiency, and primary ciliary dyskinesia were more common in those without NTM. Fifty-one percent of patients had spirometric evidence of airflow obstruction. Patients with NTM were more likely to have diffusely dilated airways and tree-in-bud abnormalities. Pseudomonas and Staphylococcus aureus isolates were cultured less commonly in patients with NTM. Bronchial hygiene measures were used more often in those with NTM, whereas antibiotics used for exacerbations, rotating oral antibiotics, steroid use, and inhaled bronchodilators were more commonly used in those without NTM. Adult patients with bronchiectasis enrolled in the US BRR are described, with differences noted in demographic, radiographic, microbiological, and treatment variables based on stratification of the presence of NTM.


The state of health in Pakistan and its provinces and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019.
Understanding health trends and estimating the burden of disease at the national and subnational levels helps policy makers track progress and identify disparities in overall health performance. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 provides comprehensive estimates for Pakistan. Comparison of health indicators since 1990 provides valuable insights about Pakistan's ability to strengthen its health-care system, reduce inequalities, improve female and child health outcomes, achieve universal health coverage, and meet the UN Sustainable Development Goals. We present estimates of the burden of disease, injuries, and risk factors for Pakistan provinces and territories from 1990 to 2019 based on GBD 2019 to improve health and health outcomes in the country. We used methods and data inputs from GBD 2019 to estimate socio-demographic index, total fertility rate, cause-specific deaths, years of life lost, years lived with disability, disability-adjusted life-years, healthy life expectancy, and risk factors for 286 causes of death and 369 causes of non-fatal health loss in Pakistan and its four provinces and three territories from 1990 to 2019. To generate estimates for Pakistan at the national and subnational levels, we used 68 location-years of data to estimate Pakistan-specific demographic indicators, 316 location-years of data for Pakistan-specific causes of death, 579 location-years of data for Pakistan-specific non-fatal outcomes, 296 location-years of data for Pakistan-specific risk factors, and 3089 location-years of data for Pakistan-specific covariates. Life expectancy for both sexes in Pakistan increased nationally from 61·1 (95% uncertainty interval [UI] 60·0-62·1) years in 1990 to 65·9 (63·8-67·8) years in 2019; however, these gains were not uniform across the provinces and federal territories. Pakistan saw a narrowing of the difference in healthy life expectancy between the sexes from 1990 to 2019, as health gains for women occurred at faster rates than for men. For women, life expectancy increased by 8·2% (95% UI 6·3-13·8) between 1990 and 2019, whereas the male life expectancy increased by 7·6% (3·5-11·8). Neonatal disorders, followed by ischaemic heart disease, stroke, diarrhoeal diseases, and lower respiratory infections were the leading causes of all-age premature mortality in 2019. Child and maternal malnutrition, air pollution, high systolic blood pressure, dietary risks, and tobacco consumption were the leading all-age risk factors for death and disability-adjusted life-years at the national level in 2019. Five non-communicable diseases-ischaemic heart disease, stroke, congenital defects, cirrhosis, and chronic kidney disease-were among the ten leading causes of years of life lost in Pakistan. Burden varied by socio-demographic index. Notably, Balochistan and Khyber Pakhtunkhwa had the lowest observed gains in life expectancy. Dietary iron deficiency was the leading cause of years lived with disability for both men and women in 1990 and 2019. Low birthweight and short gestation and particulate matter pollution were the leading contributors to overall disease burden in both 1990 and 2019 despite moderate improvements, with a 23·5% (95% UI 3·8-39·2) and 27·6% (14·3-38·6) reduction in age-standardised attributable DALY rates during the study period. Our study shows that progress has been made on reducing Pakistan's disease burden since 1990, but geographical, age, and sex disparities persist. Equitable investment in the health system, as well as the prioritisation of high-impact policy interventions and programmes, are needed to save lives and improve health outcomes. Pakistan is facing several domestic and foreign challenges-the Taliban's return to power in Afghanistan, political turmoil, catastrophic flooding, the COVID-19 pandemic-that will shape the trajectory of the country's health and development. Pakistan must address the burden of infectious disease and curb rising rates of non-communicable diseases. Prioritising these three areas will enhance Pakistan's ability to achieve universal health coverage, meet its Sustainable Development Goals, and improve the overall health outcomes. Bill & Melinda Gates Foundation. For the Urdu translation of the abstract see Supplementary Materials section.


Defect symmetry influence on electronic transport of zigzag nanoribbons.
The electronic transport of zigzag-edged graphene nanoribbon (ZGNR) with local Stone-Wales (SW) defects is systematically investigated by first principles calculations. While both symmetric and asymmetric SW defects give rise to complete electron backscattering region, the well-defined parity of the wave functions in symmetric SW defects configuration is preserved. Its signs are changed for the highest-occupied electronic states, leading to the absence of the first conducting plateau. The wave function of asymmetric SW configuration is very similar to that of the pristine GNR, except for the defective regions. Unexpectedly, calculations predict that the asymmetric SW defects are more favorable to electronic transport than the symmetric defects configuration. These distinct transport behaviors are caused by the different couplings between the conducting subbands influenced by wave function alterations around the charge neutrality point.


Parasite-induced aggression and impaired contest ability in a fish host.
Success of trophically transmitted parasites depends to a great extent on their ability to manipulate their intermediate hosts in a way that makes them easier prey for target hosts. Parasite-induced behavioural changes are the most spectacular and diverse examples of manipulation. Most of the studies have been focused on individual behaviour of hosts including fish. We suggest that agonistic interactions and territoriality in fish hosts may affect their vulnerability to predators and thus the transmission efficiency of trophically transmitted parasites. The parasite Diplostomum spathaceum (Trematoda) and juvenile rainbow trout, Oncorhynchus mykiss, were used to study whether infection can alter aggression rates and territorial behaviour of intermediate fish hosts. The changes in behaviour of rainbow trout, Oncorhynchus mykiss, infected with an eye fluke Diplostomum spathaceum (Trematoda), was monitored over the course of an experimental infection for 1.5 months. At the beginning of their development, not yet infective D. spathaceum metacercariae decreased the aggressiveness of rainbow trout. By the time that metacercariae were fully infective to their definitive hosts, the aggressiveness increased and exceeded that of control fish. Despite the increased aggressiveness, the experimentally infected fish lost contests for a territory (dark parts of the bottom) against the control fish. The results obtained indicate that the parasitized fish pay the cost of aggressiveness without the benefit of acquiring a territory that would provide them with better protection against predators. This behaviour should increase transmission of the parasite as expected by the parasite manipulation hypothesis.


The impact of RNA standardization and heterogeneous gene expression on the results of cDNA array of human breast carcinoma.
cDNA microarray is an established technique. However, difficulties such as handling tissue samples under RNase-free conditions, the heterogeneous tumor composition, i.e. non-malignant versus malignant cells and different pathologic types of malignant cells, and lack of appropriate reference may limit the potentially benefit of this method in clinical use. In this study, we examined how standardization of gene expression to total mg RNA or mg tissue and tumor heterogeneity affect the final results. We found that the gene expression of human breast tumors was approximately 9 times higher in malignant tissue as compared to the non-malignant tissue when expressed per total mg RNA, but approximately 40 times higher when expressed per mg tissue. Genes that were expected to act as housekeeping genes (PUC18, RPL and beta-actin) varied between different parts of the tumor and also between non-malignant and malignant tissues, excluding them as reference genes. We also found that the gene expression differed in various parts of the breast tumor, probably due to a mixture of different types of cells, i.e. non-malignant and malignant cells. To find out if the variations in the gene expression were due to cell heterogeneity we used microdissection to collect malignant cells separately. We found that the gene expression was markedly different in the isolated malignant cells as compared to the gene expression of the bulk tumor tissue. Thus, to be able to evaluate results from cDNA array gene expression experiments it is, to our opinion, necessary to work with pure tumor cell populations, until solid information is available on the impact of stromal component. Housekeeping genes should be handling with care and mg tissue may be preferred instead of microg RNA for standardization.


Luteolin reduces Alzheimer's disease pathologies induced by traumatic brain injury.
Traumatic brain injury (TBI) occurs in response to an acute insult to the head and is recognized as a major risk factor for Alzheimer's disease (AD). Indeed, recent studies have suggested a pathological overlap between TBI and AD, with both conditions exhibiting amyloid-beta (Aβ) deposits, tauopathy, and neuroinflammation. Additional studies involving animal models of AD indicate that some AD-related genotypic determinants may be critical factors enhancing temporal and phenotypic symptoms of TBI. Thus in the present study, we examined sub-acute effects of moderate TBI delivered by a gas-driven shock tube device in Aβ depositing Tg2576 mice. Three days later, significant increases in b-amyloid deposition, glycogen synthase-3 (GSK-3) activation, phospho-tau, and pro-inflammatory cytokines were observed. Importantly, peripheral treatment with the naturally occurring flavonoid, luteolin, significantly abolished these accelerated pathologies. This study lays the groundwork for a safe and natural compound that could prevent or treat TBI with minimal or no deleterious side effects in combat personnel and others at risk or who have experienced TBI.


Clinical Oncology Society of Australia position statement on exercise in cancer care.
Clinical research has established exercise as a safe and effective intervention to counteract the adverse physical and psychological effects of cancer and its treatment. This article summarises the position of the Clinical Oncology Society of Australia (COSA) on the role of exercise in cancer care, taking into account the strengths and limitations of the evidence base. It provides guidance for all health professionals involved in the care of people with cancer about integrating exercise into routine cancer care. Main recommendations: COSA calls for: exercise to be embedded as part of standard practice in cancer care and to be viewed as an adjunct therapy that helps counteract the adverse effects of cancer and its treatment; all members of the multidisciplinary cancer team to promote physical activity and recommend that people with cancer adhere to exercise guidelines; and best practice cancer care to include referral to an accredited exercise physiologist or physiotherapist with experience in cancer care. Changes in management as a result of the guideline: COSA encourages all health professionals involved in the care of people with cancer to: discuss the role of exercise in cancer recovery; recommend their patients adhere to exercise guidelines (avoid inactivity and progress towards at least 150 minutes of moderate intensity aerobic exercise and two to three moderate intensity resistance exercise sessions each week); and refer their patients to a health professional who specialises in the prescription and delivery of exercise (ie, accredited exercise physiologist or physiotherapist with experience in cancer care).


A wave of monocytes is recruited to replenish the long-term Langerhans cell network after immune injury.
A dense population of embryo-derived Langerhans cells (eLCs) is maintained within the sealed epidermis without contribution from circulating cells. When this network is perturbed by transient exposure to ultraviolet light, short-term LCs are temporarily reconstituted from an initial wave of monocytes but thought to be superseded by more permanent repopulation with undefined LC precursors. However, the extent to which this process is relevant to immunopathological processes that damage LC population integrity is not known. Using a model of allogeneic hematopoietic stem cell transplantation, where alloreactive T cells directly target eLCs, we have asked whether and how the original LC network is ultimately restored. We find that donor monocytes, but not dendritic cells, are the precursors of long-term LCs in this context. Destruction of eLCs leads to recruitment of a wave of monocytes that engraft in the epidermis and undergo a sequential pathway of differentiation via transcriptionally distinct EpCAM+ precursors. Monocyte-derived LCs acquire the capacity of self-renewal, and proliferation in the epidermis matched that of steady-state eLCs. However, we identified a bottleneck in the differentiation and survival of epidermal monocytes, which, together with the slow rate of renewal of mature LCs, limits repair of the network. Furthermore, replenishment of the LC network leads to constitutive entry of cells into the epidermal compartment. Thus, immune injury triggers functional adaptation of mechanisms used to maintain tissue-resident macrophages at other sites, but this process is highly inefficient in the skin.


An Exploration into Fern Genome Space.
Ferns are one of the few remaining major clades of land plants for which a complete genome sequence is lacking. Knowledge of genome space in ferns will enable broad-scale comparative analyses of land plant genes and genomes, provide insights into genome evolution across green plants, and shed light on genetic and genomic features that characterize ferns, such as their high chromosome numbers and large genome sizes. As part of an initial exploration into fern genome space, we used a whole genome shotgun sequencing approach to obtain low-density coverage (∼0.4X to 2X) for six fern species from the Polypodiales (Ceratopteris, Pteridium, Polypodium, Cystopteris), Cyatheales (Plagiogyria), and Gleicheniales (Dipteris). We explore these data to characterize the proportion of the nuclear genome represented by repetitive sequences (including DNA transposons, retrotransposons, ribosomal DNA, and simple repeats) and protein-coding genes, and to extract chloroplast and mitochondrial genome sequences. Such initial sweeps of fern genomes can provide information useful for selecting a promising candidate fern species for whole genome sequencing. We also describe variation of genomic traits across our sample and highlight some differences and similarities in repeat structure between ferns and seed plants.


Nurses' resilience and the emotional labour of nursing work: An integrative review of empirical literature.
The emotional labour of nursing work involves managing the emotional demands of relating with patients, families and colleagues. Building nurses' resilience is an important strategy in mitigating the stress and burnout that may be caused by ongoing exposure to these demands. Understandings of resilience in the context of emotional labour in nursing, however, are limited. To investigate the state of knowledge on resilience in the context of emotional labour in nursing. Integrative literature review. CINAHL, Medline, Scopus, and PsycINFO electronic databases were searched for abstracts published between 2005 and 2015 and written in English. Reference lists were hand searched. Whittemore and Knafl's integrative review method was used to guide this review. The constant comparative method was used to analyze and synthesize data from 27 peer-reviewed quantitative and qualitative articles. Methodological quality of included studies was assessed using the Mixed Methods Assessment Tool. Emotional labour is a facet of all aspects of nursing work and nurse-patient/family/collegial interactions. Emotional dissonance arising from surface acting in emotional labour can lead to stress and burnout. Resilience can be a protective process for the negative effects of emotional labour. Several resilience interventions have been designed to strengthen nurses' individual resources and reduce the negative effects of workplace stress; however they do not specifically address emotional labour. Inclusion of emotional labour-mitigating strategies is recommended for future resilience interventions. Resilience is a significant intervention that can build nurses' resources and address the effects of emotional dissonance in nursing work. There is a need for further investigation of the relationship between resilience and emotional labour in nursing, and robust evaluation of the impact of resilience interventions that address emotional labour.


Evidence-based systematic review: effects of oral motor interventions on feeding and swallowing in preterm infants.
To conduct an evidence-based systematic review and provide an estimate of the effects of oral motor interventions (OMIs) on feeding/swallowing outcomes (both physiological and functional) and pulmonary health in preterm infants. A systematic search of the literature published from 1960 to 2007 was conducted. Articles meeting the selection criteria were appraised by 2 reviewers and vetted by a 3rd for methodological quality. Twelve studies were included and focused on 3 OMIs-nonnutritive sucking (NNS), oral/perioral stimulation, and NNS plus oral/perioral stimulation. Six studies addressed the effects of OMI on the feeding/swallowing physiology outcomes of feeding efficiency or sucking pressures. Ten studies addressed the functional feeding/swallowing outcomes of oral feeding or weight gain/growth. No studies reported data on pulmonary health. Methodological quality varied greatly. NNS alone and with oral/perioral stimulation showed strong positive findings for improvement in some feeding/swallowing physiology variables and for reducing transition time to oral feeding. Prefeeding stimulation showed equivocal results across the targeted outcomes. None of the OMIs provided consistent positive results on weight gain/growth. Although some OMIs show promise for enhancing feeding/swallowing in preterm infants, methodological limitations and variations in results across studies warrant careful consideration of their clinical use.


Assessment of Fringe Pattern Decomposition with a Cross-Correlation Index for Phase Retrieval in Fringe Projection 3D Measurements.
Phase retrieval from single frame projection fringe patterns, a fundamental and challenging problem in fringe projection measurement, attracts wide attention and various new methods have emerged to address this challenge. Many phase retrieval methods are based on the decomposition of fringe patterns into a background part and a fringe part, and then the phase is obtained from the decomposed fringe part. However, the decomposition results are subject to the selection of model parameters, which is usually performed manually by trial and error due to the lack of decomposition assessment rules under a no ground truth data situation. In this paper, we propose a cross-correlation index to assess the decomposition and phase retrieval results without the need of ground truth data. The feasibility of the proposed metric is verified by simulated and real fringe patterns with the well-known Fourier transform method and recently proposed Shearlet transform method. This work contributes to the automatic phase retrieval and three-dimensional (3D) measurement with less human intervention, and can be potentially employed in other fields such as phase retrieval in digital holography.


Electrochemistry and Photoluminescence of Icosahedral Carboranes, Boranes, Metallacarboranes, and Their Derivatives.
Icosahedral boranes, carboranes, and metallacarboranes are extraordinarily robust compounds with desirable properties such as thermal and redox stability, chemical inertness, low nucleophilicity, and high hydrophobicity, making them attractive for several applications such as medicine, nanomaterials, molecular electronics, energy, catalysis, environmental chemistry, and other areas. The hydrogen atoms in these clusters can be replaced by convenient groups that open the way to a chemical alternative to conventional "organic" or "organometallic" realms. Icosahedral boron cluster derivatives have been reviewed from different perspectives; however, there is a need for a review dedicated to the redox and photophysical characteristics of easily accessible borane and carborane derivatives, which are excellent materials for a wide range of applications. This review deals with the redox properties and photoluminescence behavior of this collection of compounds, as well as their influence on the properties of materials and devices whose working principles are related to electron-transfer or electron-promotion phenomena. We hope that this review will be of great value to boron cluster scientists and researchers working in the photoluminescence and electrochemistry fields who are interested in exploring the possibilities of these unique and promising systems.


Isolation and structural elucidation of pentacyclic triterpenoids from Maprounea africana.
Pentacyclic triterpenoids based on the taraxer-14-ene skeleton with a C-28 attached carboxylic acid group have been isolated from the roots of Maprounea africana. These compounds were identified as 1 beta,2 alpha-dihydroxyaleuritolic acid 2,3-bis-p-hydroxybenzoate [1], 2 alpha-hydroxyaleuritolic acid 3-p-hydroxybenzoate [2], 2 alpha-hydroxyaleuritolic acid 2,3-bis-p-hydroxybenzoate [4], aleuritolic acid 3-p-hydroxybenzoate [5], aleuritolic acid [6], and aleuritolic acid 3-acetate [7]. Compounds 1 and 2 are new triterpene esters. Compound 3 was previously reported as 7 beta-hydroxymaprounic acid 3-p-hydroxybenzoate [13]. However, based on detailed nmr studies, its structure has been revised.


Early Distraction for Mild to Moderate Unilateral Craniofacial Microsomia: Long-Term Follow-Up, Outcomes, and Recommendations.
There is controversy regarding the treatment of young patients with unilateral craniofacial microsomia and moderate dysmorphism. The relative indication for mandibular distraction in such patients poses several questions: Is it deleterious in the context of craniofacial growth and appearance? This study was designed to address these questions. A retrospective review of patients undergoing mandibular distraction by a single surgeon between 1989 and 2010 was conducted. Patients with "moderate" unilateral craniofacial microsomia (as defined by Pruzansky type I or IIa mandibles) and follow-up until craniofacial skeletal maturity were included for analysis. Patients were divided into two cohorts: satisfactory and unsatisfactory results based on photographic aesthetic evaluation by independent blinded observers at the initial presentation and at the age of skeletal maturity. Clinical variables were analyzed to detect predictors for satisfactory distraction. Nineteen patients were included for analysis. The average age at distraction was 68.2 months and the average age at follow-up was 19.55 years. Thirteen patients (68.4 percent) had Pruzansky type IIA and six patients (31.6 percent) had Pruzansky type I mandibles. Twelve patients (63.2 percent) had satisfactory outcomes, whereas seven patients (36.8 percent) had unsatisfactory outcomes. Comparing the two cohorts, patients with satisfactory outcomes had distraction at an earlier age (56.4 months versus 89.8 months; p = 0.07) and a greater percentage overcorrection from craniofacial midline (41.7 percent versus 1.8 percent; p = 0.003). Mandibular distraction is successful in patients with mild to moderate dysmorphism, provided that there is a comprehensive clinical program emphasizing adequate mandibular bone stock, proper vector selection, planned overcorrection, and comprehensive orthodontic management. Therapeutic, III.


Factors associated with acceptability of child circumcision in Botswana -- a cross sectional survey.
Safe male child circumcision has been recently adopted as a potential strategy to prevent HIV/AIDS transmission in later life in Botswana. Data used was derived from a cross-sectional survey, the Botswana AIDS Impact Survey (BAIS) IV, conducted in 2013. A total sample of 7984 respondents in ages 15-64 years who had successfully completed the individual questionnaire during the survey were selected and included for analysis. Both descriptive and multivariable analyses were used to explore factors associated with acceptability of child circumcision. Data was analysed using SPSS version 22 program. Results indicate that about 84 % of participants said they would circumcise their male children aged 18 years and below, while 93 % were aware of the safe male circumcision program. Bivariate analyses results show that acceptability of child circumcision was significantly associated with sex, age, education, religion, residence, HIV status of the parent, fathers circumcision status, father's intention to circumcise and parent's knowledge about the safe male circumcision program. Multivariable analyses results indicate positive association between respondent's HIV positive status (OR, 3.5), Men's circumcision status (OR, 3.7), men's intention to circumcise (OR, 9.3) and acceptability of child circumcision. Results of this study indicate some relatively high acceptability levels for child circumcision. Some individual behavioural factors influencing acceptability of child circumcision were also identified. This study provides a proper understanding of factors associated with acceptability of child circumcision which will ultimately enhance the successful roll-out of the school going children circumcision program in Botswana.


Long-distance control of synapse assembly by target-derived NGF.
We report a role for long-distance retrograde neurotrophin signaling in the establishment of synapses in the sympathetic nervous system. Target-derived NGF is both necessary and sufficient for formation of postsynaptic specializations on dendrites of sympathetic neurons. This, in turn, is a prerequisite for formation of presynaptic specializations, but not preganglionic axonal ingrowth from the spinal cord into sympathetic ganglia. We also find that NGF-TrkA signaling endosomes travel from distal axons to cell bodies and dendrites where they promote PSD clustering. Furthermore, the p75 neurotrophin receptor restricts PSD formation, suggesting an important role for antagonistic NGF-TrkA and p75 signaling pathways during retrograde control of synapse establishment. Thus, in addition to defining the appropriate number of sympathetic neurons that survive the period of developmental cell death, target-derived NGF also exerts control over the degree of connectivity between the spinal cord and sympathetic ganglia through retrograde control of synapse assembly.


Prevention of postpartum hemorrhage in low-resource settings: current perspectives.
Postpartum hemorrhage (PPH) is the leading cause of maternal death in low-income countries and is the primary cause of approximately one-quarter of global maternal deaths. The purpose of this paper is to provide a review of PPH prevention interventions, with a particular focus on misoprostol, and the challenges and opportunities that preventing PPH in low-resource settings presents. Using PubMed, we conducted a review of the literature on the randomized controlled trials of interventions to prevent PPH. We then searched PubMed and Google Scholar for nonrandomized field trials of interventions to prevent PPH. We limited our review to interventions that are discussed in the current World Health Organization (WHO) recommendations for PPH prevention and present evidence regarding the use of these interventions. We focused our review on nondrug PPH prevention interventions compared with no intervention and uterotonics versus placebo; this review does not decipher the relative effectiveness of uterotonic drugs. We describe challenges to and opportunities for scaling up PPH prevention interventions. Active management of the third stage of labor is considered the "gold standard" strategy for reducing the incidence of PPH. It combines nondrug interventions (controlled cord traction and cord clamping) with the administration of an uterotonic drug, the preferred uterotonic being oxytocin. Unfortunately, oxytocin has limited application in resource-poor countries, due to its heat instability and required administration by a skilled provider. New heat-stable drugs and drug formulations are currently in development that may improve the prevention of PPH; however, misoprostol is a viable option for provision at home by a lay health care worker or the woman herself, in the interim. As the main cause of maternal mortality worldwide, PPH prevention interventions need to be prioritized. Increased access to prophylactic uterotonics, regardless of where deliveries occur, should be the primary means of reducing the burden of this complication.


An automated technique to identify potential inappropriate traditional Chinese medicine (TCM) prescriptions.
Medication errors such as potential inappropriate prescriptions would induce serious adverse drug events to patients. Information technology has the ability to prevent medication errors; however, the pharmacology of traditional Chinese medicine (TCM) is not as clear as in western medicine. The aim of this study was to apply the appropriateness of prescription (AOP) model to identify potential inappropriate TCM prescriptions. We used the association rule of mining techniques to analyze 14.5 million prescriptions from the Taiwan National Health Insurance Research Database. The disease and TCM (DTCM) and traditional Chinese medicine-traditional Chinese medicine (TCMM) associations are computed by their co-occurrence, and the associations' strength was measured as Q-values, which often referred to as interestingness or life values. By considering the number of Q-values, the AOP model was applied to identify the inappropriate prescriptions. Afterwards, three traditional Chinese physicians evaluated 1920 prescriptions and validated the detected outcomes from the AOP model. Out of 1920 prescriptions, 97.1% of positive predictive value and 19.5% of negative predictive value were shown by the system as compared with those by experts. The sensitivity analysis indicated that the negative predictive value could improve up to 27.5% when the model's threshold changed to 0.4. We successfully applied the AOP model to automatically identify potential inappropriate TCM prescriptions. This model could be a potential TCM clinical decision support system in order to improve drug safety and quality of care.


Maternal blood arsenic levels and associations with birth weight-for-gestational age.
Among highly exposed populations, arsenic exposure in utero may be associated with decreased birth weight, however less is known about potential effects of arsenic exposure in urban communities without contaminated sources such as drinking water. Investigate the association of blood arsenic levels with birth weight-for-gestational age categories within a prospective birth cohort study. We analyzed 730 mother-infant dyads within the Programming Research in Obesity, GRowth, Environment and Social Stressors (PROGRESS) cohort in Mexico City. Total arsenic was measured in maternal blood samples from the 2nd and 3rd trimesters, at delivery, as well as from infant umbilical cord blood samples. Multivariable, multinomial logistic regression models adjusting for maternal age at enrollment, pre-pregnancy body mass index, parity, infant sex, socioeconomic position, and prenatal environmental tobacco smoke exposure were used to calculate odds ratios of small-for-gestational age (<10th percentile, SGA) and large-for-gestational age (>90th percentile, LGA) compared to appropriate-for-gestational age (AGA) per unit increase of log-transformed arsenic. Median (IQR) blood arsenic levels for maternal second trimester were 0.72 (0.33) μg/L, maternal third trimester 0.75 (0.41) μg/L, maternal at delivery 0.85 (0.70) μg/L, and infant cord 0.78 (0.65) μg/L. Maternal delivery and infant cord blood samples were most strongly correlated (spearman r = 0.65, p < 0.0001). Maternal arsenic levels at delivery were associated with significantly higher odds of both SGA (adj. OR = 1.44, 95% CI: 1.08-1.93) and LGA (adj. OR = 2.03, 95% CI: 1.12-3.67) compared to AGA. Results were similar for cord blood. There were 130 SGA infants and 22 LGA infants. Earlier in pregnancy, there were no significant associations of arsenic and birth weight-for-gestational age. However, we observed non-significantly higher odds of LGA among women with higher arsenic levels in the 3rd trimester (adj. OR = 1.46, 95% CI: 0.67-3.12). We found that in a Mexico City birth cohort, higher maternal blood arsenic levels at delivery were associated with higher odds of both SGA and LGA. However, sources and species of arsenic were not known and the number of LGA infants was small, limiting the interpretation of this finding and highlighting the importance of future large studies to incorporate arsenic speciation. If our findings were confirmed in studies that addressed these limitations, determining modifiable factors that could be mitigated, such as sources of arsenic exposure, may be important for optimizing fetal growth to improve long-term health of children.


Relationship of autoimmunity to thyroid dysfunction in children and adults with Down syndrome.
The extent to which autoimmunity contributes to thyroid dysfunction in Down Syndrome (DS) individuals has not been clarified. We studied 61 persons (34 males and 27 females) with DS (age 5 months to 48 years) for the presence of thyroid autoantibodies (thyroid microsomal antibodies and thyroglobulin antibodies), pancreatic islet cell autoantibodies, gastric parietal cell autoantibodies, and adrenocortical autoantibodies. Thyroid function was determined by measurement of TSH. HLA-A, B and -DR typing was performed on 52 subjects. Forty of 61 subjects (66%) had thyroid dysfunction: elevated TSH values (greater than 5 mcIU/ml) were found in 35 of 61 individuals; 3 subjects had previously documented Hashimoto thyroiditis and were on therapy for hyperthyroidism; and 2 persons had Graves disease. No age or sex variation was detected. Seventeen (28%) subjects had thyroid autoantibodies. Fifteen of the 17 had thyroid dysfunction. Twelve of 25 subjects (48%) over 10 years with thyroid dysfunction had thyroid autoantibodies compared to only 3 of 15 (20%) under the age of 10 years. However, children less than of 10 years tended to have higher TSH values. Only 1 individual who had thyroid antibodies had gastric parietal cell autoantibodies present. Islet cell and adrenocortical autoantibodies were not found in any individuals. Neither thyroid dysfunction nor thyroid autoantibodies correlated with any HLA allele. These findings suggest that thyroid dysfunction in individuals with DS of all ages is a common heterogeneous disorder which cannot be solely explained on the basis of autoimmunity. We recommend that thyroid function be followed closely whether or not thyroid autoantibodies are present.


Evaluation of a quality assurance program for quantitation of human immunodeficiency virus type 1 RNA in plasma by the AIDS Clinical Trials Group virology laboratories.
A number of quantitative assays have been developed by using amplification techniques to measure human immunodeficiency virus type 1 RNA in the plasma of infected individuals. The Virology Committee of the AIDS Clinical Trials Group in the Division of AIDS, National Institute of Allergy and Infectious Diseases, has established a quality assurance program (QAP) for quantitative assays of HIV-1 RNA levels in plasma. The primary objective of the QAP was to ascertain that a laboratory could maintain the precision required to have a 90% power to detect a fivefold difference in RNA copy number between two samples in the same batch. To achieve this goal, the QAP required an intra-assay standard deviation of no greater than 0.15 log10 RNA copies per ml. Panels for proficiency testing consisted of coded replicate samples and a common set of standards. To date, 41 laboratories have participated in the program and have used both commercial and in-house assays. We demonstrated that 65% of the laboratories were capable of attaining the necessary level of intra-assay precision. The fitted regressions indicated that the differences among laboratories that used the same kit were generally greater than the differences among population-average regressions for the kits themselves. The use of an external QAP and a common set of standards reduced differences both among laboratories that used the same kit and among laboratories that used different kits. Thus, use of a common set of standards across clinical trial protocols would allow for cross-protocol comparisons.


Association Between Chronic Health Conditions and Quality of Life in Rural Teachers.
The school teacher profession has been reported to be associated with an increased rate of health problems that can affect the quality of life (QoL) of teachers. However, there is little information about rural teachers. To investigate the associations of obesity, abdominal obesity, and hypertension with the perception of QoL in rural teachers. This cross-sectional study included a representative sample of teachers from eight rural schools in the Valparaíso Region of Chile. Obesity was evaluated by the percentages of fat mass (% FM) and abdominal obesity, and hypertension was recorded. The Short Form-36 Health Survey was administered to subjects to evaluate QoL. A logistic regression adjusted for age and gender was used to associate QoL with chronic health conditions. Eighty-five percent of teachers presented abdominal obesity, 56% presented obesity evaluated by % FM and 33% presented hypertension. Thirty percent of teachers in the ≥45-year-old age group presented all three chronic conditions simultaneously. Teachers presenting abdominal obesity in the ≤44-year-old age group had lower scores in the mental health component (MCS) (p < 0.05) of the survey than the teachers in the ≥45-year-old age group. In addition, teachers in the ≤44-year-old age group who presented obesity scored lower in the MCS than those in the same age group without obesity (p = 0.004). The occurrence simultaneous of two and three chronic health conditions increased the risk of reduced MCS significantly (p = 0.015, OR 17.0, 95% CI: 1.741-165.90 and p = 0.003, OR 82.6, 95% CI: 4.58-1490.70, respectively). In addition, ages under 45 years old were associated with low score of MCS (OR 8.8, 95% CI: 1.565-49.698). A combination of chronic conditions affects the mental health (MH) of rural teachers. Although the association does not imply causation, these findings support the notion that teachers present early MH problems. This suggests that resources must be made available to detect early mental and chronic health conditions of rural teachers.


Gene expression of porcine blastocysts from gilts fed organic or inorganic selenium and pyridoxine.
In this study, we determined how maternal dietary supplementation with pyridoxine combined with different sources of selenium (Se) affected global gene expression of porcine expanded blastocysts (PEB) during pregnancy. Eighteen gilts were randomly assigned to one of the three experimental diets (n=6 per treatment): i) basal diet without supplemental Se or pyridoxine (CONT); ii) CONT+0.3 mg/kg of Na-selenite and 10 mg/kg of HCl-pyridoxine (MSeB610); and iii) CONT+0.3 mg/kg of Se-enriched yeast and 10 mg/kg of HCl-pyridoxine (OSeB610). All gilts were inseminated at their fifth post-pubertal estrus and killed 5 days later for embryo harvesting. A porcine embryo-specific microarray was used to detect differentially gene expression between MSeB610 vs CONT, OSeB610 vs CONT, and OSeB610 vs MSeB610. CONT gilts had lower whole blood Se and erythrocyte pyridoxal-5-P concentrations than supplemented gilts (P<0.05). No treatment effect was observed on blood plasma Se-glutathione peroxidase activity (P=0.57). There were 10, 247, and 96 differentially expressed genes for MSeB610 vs CONT, OSeB610 vs CONT, and OSeB610 vs MSeB610 respectively. No specific biological process was associated with MSeB610 vs CONT. However, for OSeB610 vs CONT, upregulated genes were related with global protein synthesis but not to selenoproteins. The stimulation of some genes related with monooxygenase and thioredoxin families was confirmed by quantitative real-time RT-PCR. In conclusion, OSeB610 affects PEB metabolism more markedly than MSeB610. Neither Se sources with pyridoxine influenced the Se-glutathione peroxidase metabolic pathway in the PEB, but OSeB610 selectively stimulated genes involved with antioxidant defense.


High resolution HLA haplotyping by imputation for a British population bioresource.
This study aimed to establish the occurrence and frequency of HLA alleles and haplotypes for a healthy British Caucasian population bioresource from Oxfordshire. We present the results of imputation from HLA SNP genotyping data using SNP2HLA for 5553 individuals from Oxford Biobank, defining one- and two-field alleles together with amino acid polymorphisms. We show that this achieves a high level of accuracy with validation using sequence-specific primer amplification PCR. We define six- and eight-locus HLA haplotypes for this population by Bayesian methods implemented using PHASE. We determine patterns of linkage disequilibrium and recombination for these individuals involving classical HLA loci and show how analysis within a haplotype block structure may be more tractable for imputed data. Our findings contribute to knowledge of HLA diversity in healthy populations and further validate future large-scale use of HLA imputation as an informative approach in population bioresources.


Interdisciplinary insights on the future of food systems research: perspectives from the next generation of research leaders.
Our dominant food system is a primary driver of worsening human and planetary health. Held in March 2022, the Public Health Association of Australia's Food Futures Conference was an opportunity for people working across the food system to connect and advocate for a comprehensive, intersectoral, whole-of-society food and nutrition policy in Australia to attenuate these issues. Conference themes included food systems for local and global good; ecological nutrition; social mobilisation for planetary and public good; food sovereignty and food equity. Students and young professionals are integral in transforming food systems, yet they are under-represented in the academic workforce, across publishing, scientific societies and conference plenaries. A satellite event was held to platform initiatives from early career researchers (ECR) in areas integral for improving planetary and public good. The research topics discussed in this commentary reflect sub-themes of the conference under investigation by ECR: food systems governance and regulation; local food policies; commercial determinants of health; sustainable healthy diets; and food equity and sovereignty.


A neurodevelopmental origin of behavioral individuality in the Drosophila visual system.
The genome versus experience dichotomy has dominated understanding of behavioral individuality. By contrast, the role of nonheritable noise during brain development in behavioral variation is understudied. Using Drosophila melanogaster, we demonstrate a link between stochastic variation in brain wiring and behavioral individuality. A visual system circuit called the dorsal cluster neurons (DCN) shows nonheritable, interindividual variation in right/left wiring asymmetry and controls object orientation in freely walking flies. We show that DCN wiring asymmetry instructs an individual's object responses: The greater the asymmetry, the better the individual orients toward a visual object. Silencing DCNs abolishes correlations between anatomy and behavior, whereas inducing DCN asymmetry suffices to improve object responses.


Shigella depends on SepA to destabilize the intestinal epithelial integrity via cofilin activation.
Shigella is unique among enteric pathogens, as it invades colonic epithelia through the basolateral pole. Therefore, it has evolved the ability to breach the intestinal epithelial barrier to deploy an arsenal of effector proteins, which permits bacterial invasion and leads to a severe inflammatory response. However, the mechanisms used by Shigella to regulate epithelial barrier permeability remain unknown. To address this question, we used both an intestinal polarized model and a human ex-vivo model to further characterize the early events of host-bacteria interactions. Our results showed that secreted Serine Protease A (SepA), which belongs to the serine protease autotransporter of Enterobacteriaceae family, is responsible for critically disrupting the intestinal epithelial barrier. Such disruption facilitates bacterial transit to the basolateral pole of the epithelium, ultimately fostering the hallmarks of the disease pathology. SepA was found to cause a decrease in active LIM Kinase 1 (LIMK1) levels, a negative inhibitor of actin-remodeling proteins, namely cofilin. Correspondingly, we observed increased activation of cofilin, a major actin-polymerization factor known to control opening of tight junctions at the epithelial barrier. Furthermore, we resolved the crystal structure of SepA to elucidate its role on actin-dynamics and barrier disruption. The serine protease activity of SepA was found to be required for the regulatory effects on LIMK1 and cofilin, resulting in the disruption of the epithelial barrier during infection. Altogether, we demonstrate that SepA is indispensable for barrier disruption, ultimately facilitating Shigella transit to the basolateral pole where it effectively invades the epithelium.


Looking proximally and distally: 100 years of limb regeneration and beyond.
The experimental study of amphibian limb regeneration spans most of the 20th century and the first decade of the 21st century. We first review the major questions investigated over this time span: (1) the origin of regeneration blastema cells, the mechanism of tissue breakdown that liberates cells from their tissue organization to participate in blastema formation, (3) the mechanism of dedifferentiation of these cells, (4) how the blastema grows, (5) how the blastema is patterned to restore the missing limb structures, and (6) why adult anurans, birds and mammals do not have the regenerative powers of urodele salamanders. We then look forward in a perspective to discuss the many unanswered questions raised by investigations of the past century, what new approaches can be taken to answer them, and what the prospects are for translation of basic research on limb regeneration into clinical means to regenerate human appendages.


Long-term outcomes of the Boston type I keratoprosthesis in eyes with previous herpes simplex virus keratitis.
To report the long-term outcomes of the Boston type I keratoprosthesis (Kpro) in eyes with prior herpes simplex virus (HSV) keratitis. Retrospective review of all Kpro procedures performed by a single surgeon from 1 May 2004 to 1 January 2015. 13 of 173 Kpro procedures were performed in 11 eyes with prior HSV keratitis. There was not a significant difference in the percentage of eyes with and without prior HSV keratitis with preoperative (9% vs 8%, p=1.00) or postoperative (57% vs 60%, p=1.00) corrected distance visual acuity (CDVA) ≥20/200 or in the percentage of contralateral eyes with preoperative CDVA ≥20/50 (55% vs 30%, p=0.18). While several postoperative complications occurred approximately twice as often in eyes with prior HSV keratitis, including persistent epithelial defect (63.6% vs 34.1%; p=0.10), corneal infiltrate (27.3% vs 12.3%; p=0.17) and sterile vitritis (18.2% vs 9.4%; p=0.31), only cystoid macular oedema (45.5% vs 12.3%; p=0.01) was significantly more common. Similarly, while the Kpro retention failure rate in eyes with prior HSV keratitis was twice than that in eyes without it (0.15 vs 0.07 per year), the difference was not statistically significant (p=0.09). As greater than half of patients with unilateral HSV keratitis undergoing Kpro implantation have CDVA ≥20/50 in the contralateral eye, and as the Kpro retention failure rate in eyes with prior HSV keratitis is twice than that in eyes without prior HSV keratitis, caution should be exercised when considering Kpro implantation in these patients.


Assessing the Fatty Acid, Carotenoid, and Tocopherol Compositions of Amaranth and Quinoa Seeds Grown in Ontario and Their Overall Contribution to Nutritional Quality.
Various fatty acids, tocopherols, carotenoids, and their respective antioxidant contributions in 7 amaranth seed and 11 quinoa seed samples along with a new evaluation method are reported. The lipid yield was 6.98-7.22% in amaranth seeds and 6.03-6.74% in quinoa seeds, with unsaturated fatty acids (UFAs) being the predominant fatty acids, 71.58-72.44% in amaranth seeds and 81.44-84.49% in quinoa seeds, respectively. Carotenoids, mainly lutein and zeaxanthin, are confirmed for the first time in amaranth seeds, while β-carotene is reported first in quinoa seeds. The predominant tocopherols in amaranth seeds are δ- and α-tocopherol, whereas γ- and α-tocopherol are the primary tocopherols in quinoa seeds. UFAs, carotenoids, and tocopherols showed good correlation with antioxidant activity. All of the amaranth seeds demonstrated lower overall lipophilic quality than quinoa seeds, with the AS1 and QS10 cultivars providing the highest scores for amaranth and quinoa seeds, respectively. Results from this study will contribute to developing quinoa seeds and related functional foods with increased benefits.


Heart-type fatty acid binding protein as an early marker for myocardial infarction: systematic review and meta-analysis.
Heart-type fatty acid binding protein (H-FABP) has been proposed as an early biomarker of myocardial infarction (MI). The authors aimed to undertake a systematic review and meta-analysis to estimate the early sensitivity and specificity of quantitative and qualitative H-FABP assays. The authors undertook a systematic search using electronic databases, citation lists and expert contacts to identify all diagnostic cohort studies of patients presenting with suspected acute coronary syndrome that compared H-FABP at presentation to a reference standard based on the Universal definition of MI. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies tool. Meta-analysis was conducted using Bayesian Markov chain Monte Carlo simulation. The authors included eight studies of quantitative H-FABP and nine studies of qualitative H-FABP. The summary estimates of sensitivity and specificity were 81% (95% prediction interval 50% to 95%) and 80% (26% to 98%) respectively for the quantitative assays and 68% (11% to 97%) and 92% (20% to 100%) respectively for the qualitative assays. Four studies reported the sensitivity of troponin and H-FABP at presentation in which the combination was considered positive if either test was positive. The addition of H-FABP to troponin increased sensitivity from 42-75% to 76-97% but decreased specificity from 94-100% to 65-93%. H-FABP has modest sensitivity and specificity for MI at presentation but estimates are subject to substantial uncertainty and primary data are subject to substantial heterogeneity. H-FABP may have a role alongside troponin in improving early sensitivity but comparison with high sensitivity troponin assays is required.


Uricosuric agents in uremic sera. Identification of indoxyl sulfata and hippuric acid.
Serum and urine from chronically uremic patients and normal individuals were subjected to gel filtration of Sephadex-G10. The effects of the eluted fractions on the uptake of urate and para-aminohippurate by isolated cortical tubules of rabbit kidney were investigated. According to the origin of the samples, one to three major groups of fractions inhibiting both urate and para-aminohippurate transport were disclosed. The first eluted group occurred for all the samples under study. The second one was demonstrated in both sera and urines from uremic patients but only in urines from normal individuals. The third one was exclusively detected in uremic sera and urines. Among all the compounds identified, only hippuric acid, eluted in the fractions of the second group, was capable of inhibiting the uptake of urate and para-aminohippurate in vitro. The concentration for which this inhbiitory effect of hippuric acid occurred was in the range of that existing in uremic sera. Indoxyl sulfate, which accumulates to very high concentrations in uremic serum, could not be disclosed in the above-mentioned fractions. This is explained by the strong adsorption of this indole derivative to Sephadex gel. Potassium indoxyl sulfate, when tested in vitro at the concentration existing in uremic serum, substantially inhibited the uptake of both urate and para-aminohippurate. In normal subjects, ingestion of hippuric acid or potassium indoxyl sulfate significantly increased fractional urinary excretion of uric acid. On the basis of these results, it is suggested that progressive retention of hippuric acid, indoxyl sulfate, and other yet unidentified inhibitors may explain the gradual increase in urinary fractional excretion of urate observed in uremia. The present results may be viewed as an example of a mechanism in which retention of normally excreted end products is responsible for adaptation of tubular transport in uremic subjects.


Opportunities for technology-based HIV prevention programming among high school students in Cape Town, South Africa.
One in three new cases of HIV in South Africa is among adolescents. Given that adolescents are particularly affected, scalable, and cost-effective prevention programs are urgently needed. This study aims to identify opportunities to integrate technology into youth HIV prevention efforts. In 2012, 1107 8th-11th graders completed a paper-and-pencil survey. Respondents were enrolled in one of three public high schools in Langa, a lower income community in Cape Town, South Africa. Eighty-nine percent of respondents have used text messaging (SMS) and 86% have gone online. If an HIV prevention program was offered online, 66% of youth would be somewhat or extremely likely to access it; slightly fewer (55%) felt the same about SMS-based programming. In comparison, 85% said they would be somewhat or extremely likely to access a school-based HIV prevention program. Interest in Internet- (60%) and SMS-based (54%) HIV prevention programming was similar for youth who had a self-appraised risk of HIV compared to youth who appraised their risk to be lower, as it was for youth who were tired of hearing messages about HIV prevention. Technology use is common - even among high school students who live in lower income communities. At the same time, these data reveal that it is not uncommon for youth to be tired of hearing messages about HIV prevention, and many of the typical topics key to HIV prevention have low interest levels among youth. HIV prevention researchers need to be mindful of the extent of existing programming that youth are exposed to. Technology-based programming may be especially amenable to meeting these requirements because of its novelty especially in developing countries, and because interactive functionality can be easily integrated into the program design. Given the preference for school- and Internet-based programming, it seems that a hybrid approach is likely feasible and acceptable.


The Manchester Color Wheel: development of a novel way of identifying color choice and its validation in healthy, anxious and depressed individuals.
For the purposes of our research programme we needed a simple, reliable and validated method for allowing choice of a color in response to a series of questions. On reviewing the literature no such instrument was available and this study aimed to rectify this situation. This was achieved by developing a simple method of presenting a series of colors to people validating it in healthy volunteers and in individuals where color choice might be distorted, namely anxiety and depression. A series of different presentations of four shades of eight colors and grey, as well as black and white were evaluated. 'Mood', 'favourite' and 'drawn to' colors were assessed in 105 healthy, 108 anxious and 110 depressed participants. The positive, neutral or negative attribution of these colors was recorded in a further 204 healthy volunteers. The circular presentation of colors was most favoured (Color Wheel). Yellow was the most 'drawn to' color and blue the commonest 'favourite' color in all subjects. Yellow was most often associated with a normal mood and grey with an anxious or depressed mood. Different shades of the same color had completely different positive or negative connotations. Reproducibility was exceptionally high when color choice was recorded in positive, neutral or negative terms. The Color Wheel could be used to assess health status, mood or even treatment outcome in a variety of clinical situations. It may also have utility in circumstances where verbal communication may not be optimal, such as with children.


Lessons from disaster: Creating a business continuity plan that really works.
Business Continuity Planning (BCP) is well established as a key plank in an organisation's risk management process. But how effective is BCP when disaster strikes? This paper examines the experiences of organisations following the 2010-11 Canterbury, New Zealand earthquakes. The study finds that BCP was helpful for all organisations interviewed but more attention is needed on the management of societal and personal impacts; development of employee resilience, identification of effective crisis leaders; right-sizing plans and planning to seize opportunities post-disaster.


Malaria parasitaemia among pregnant women in a rural community of eastern Nigeria; need for combined measures.
Malaria in pregnancy is a major contributor to adverse maternal and perinatal outcome. In hyper endemic areas like ours, it is a common cause of anaemia in pregnancy in both immune and non-immune individuals and is aggravated by poor socioeconomic circumstances. The aim of this study is to assess the prevalence of asymptomatic malaria parasitaemia among pregnant women in a rural setting. 272 pregnant women, aged between 18 and 40 years in some remote rural areas of Ebonyi State, Nigeria were recruited between January 2007 and March 2008.Their blood samples were collected and examined for malaria parasite, haemoglobin and packed cell volume using standard methods. Our results showed 59.9% prevalence of parasitaemia with the highest prevalence occurring in the first trimester [84.1%]. Among the positive cases, mild parasitaemia was recorded in 47.2% moderate parasitaemia in 37.4% while severe parasitaemia was recorded in 15.3% of cases. These differences were statistically significant [P<0.016]. Furthermore the distribution of malaria densities in different gravidity groups showed an inverse relationship, 45.4% in primigravidae, [31.9%] in secundigravidae and [10.4%] among people with more than five pregnancies. These findings were statistically significant [P<0.0001]. The prevalence of anaemia in pregnancy in this study was 62.4%. Apart from the use of nets, drugs and vector control, the prevention of malaria in pregnancy in very poor socioeconomic settings should make provision for nutritional support.