Unusual structural features of hydantoin lesions translate into efficient recognition by Escherichia coli Fpg.
Oxidation of guanine (G) and 8-oxoguanine (OG) with a wide variety of oxidants yields the hydantoin lesions, guanidinohydantoin (Gh) and spiroiminodihydantoin (Sp). These two lesions have garnered much recent attention due to their unusual structures and high mutagenic potential. We have previously shown that duplexes containing Gh and Sp are substrates for the base excision repair glycosylase Escherichia coli Fpg (EcFpg). To evaluate the recognition features of these unusual lesions, binding and footprinting experiments were performed using a glycosylase inactive variant, E3Q EcFpg, and 30 bp duplexes containing the embedded lesions. Surprisingly, E3Q EcFpg was found to bind significantly more tightly ( approximately 1000-fold) to duplexes containing Gh or Sp over the corresponding duplexes containing OG. This may be a consequence of the helix-destabilizing nature of the hydantoin lesions that facilitates their recognition within duplex DNA. Though DNA binding affinities of E3Q EcFpg with Gh- and Sp-containing duplexes were found to be similar to each other, hydroxyl radical footprinting using methidium-propyl-EDTA (MPE)-Fe(II) revealed subtle differences between binding of E3Q EcFpg to the two lesions. Most notably, in the presence of E3Q EcFpg, the Sp nucleotide (nt) is hyperreactive toward cleavage by MPE-Fe(II)-generated hydroxyl radicals, suggestive of the formation of an intercalation site for the MPE-Fe(II) reagent at the Sp nt. Interestingly, increasing the duplex length from 18 to 30 bp enhanced the excision efficiency of Gh and Sp paired with C, G, or T by EcFpg such that these substrates are processed as efficiently as the signature substrate lesion, OG. Moreover, the base removal activity with these two lesions was more efficient than removal of OG when in a base pairing context opposite A. The high affinity and efficient activity of EcFpg toward the hydantoin lesions suggest that EcFpg mediates repair of the lesions in vivo. Notably, the facile activity of EcFpg toward Gh and Sp in base pairing contexts with G and A, which are likely to be present after DNA replication, would be detrimental and enhance mutagenesis.


Azathioprine hepatotoxicity after liver transplantation.
We report the first two cases of apparent azathioprine hepatotoxicity occurring after liver transplantation. The two patients exhibited jaundice, elevated serum transaminase activities and histopathological features of sinusoidal congestion and centrilobular hepatocellular degeneration 17 and 61 days after transplantation. After withdrawal of azathioprine, liver test results improved immediately in both patients. Recurrence of liver injury after another challenge with azathioprine was seen in the first case. Previously, fatal venoocclusive disease occurring after kidney transplantation had been attributed to azathioprine. Irreversible venoocclusive disease and the reversible hepatotoxicity described in this report (i.e., sinusoidal congestion with centrizonal necrosis) most likely represent different stages of hepatic endotheliitis caused by azathioprine. Thus early diagnosis of azathioprine hepatotoxicity is of great importance.


Efficacy and safety of bevacizumab in progressive pediatric low-grade glioma: a systematic review and meta-analysis of outcome rates.
Successful management of pediatric low-grade glioma (pLGG) can be complicated by eloquent anatomical location, as well as specific pathologic and molecular features. Some authors have proposed using the VEGF inhibitor bevacizumab to improve disease control, but its safety and efficacy are poorly defined. Correspondingly, our aim was to pool systematically identified clinical data in the literature to assess the clinical utility of bevacizumab for pLGG at progression. A systematic search of 7 electronic databases from inception to June 2019 was conducted following PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines. Articles were screened against prespecified criteria. Outcomes were then pooled by random-effects meta-analyses of proportions. Seven pertinent studies described the outcomes of 110 progressive pLGG patients managed with bevacizumab in largely multiagent regimens. While on treatment, the rate of clinical response was 58% (95% CI, 43%-72%), and the rate of response on imaging was 80% (95% CI, 58%-96%). The rate of grade 3 or higher toxicity was 8% (95% CI, 2%-17%), with proteinuria the most commonly described. In the off-treatment period up to median 1 year, the rate of progression was estimated to be 51% (95% CI, 28%-74%). Bevacizumab has the potential to control clinical and radiographic disease with relatively low grade 3 or higher toxicity risk in progressive pLGG patients. However, the long-term off-treatment benefits of this therapy are not yet well defined. Heterogeneity in the literature precludes any formal recommendations regarding its use until larger, more standardized investigations can be performed.


Ischemic fasciitis: analysis of 44 cases indicating an inconsistent association with immobility or debilitation.
Ischemic fasciitis is a rare pseudosarcomatous proliferation of atypical fibroblasts described to be located over bony protuberances and said to develop most often in immobile elderly or debilitated patients. We report the clinicopathologic features of 44 cases of this pseudosarcomatous reactive fibroblastic/myofibroblastic proliferation. There were 15 female and 29 male patients between 23 and 96 years of age (median: 74 y). Tumor size, known in 34 cases, ranged from 1.3 to 10 cm (median: 4.7 cm). The lesions developed mostly in the deep subcutis (27 cases) and infiltration of deep dermis, muscle, and tendinous tissue was sometimes observed. In 3 cases, the lesion developed within skeletal muscle. In 33 cases (76.7%), the tumor was located around the limb girdles and sacral region; 5 tumors each (23.3%) occurred on the chest wall and the back. A history of physical debilitation could be confirmed in only 7 patients. Nine patients had a history of chronic or malignant diseases and 4 patients had a history of local trauma. The histologic hallmark of this reactive proliferation is a zonal appearance with central fibrinoid degeneration/necrosis and cystic changes surrounded by a granulation tissuelike vascular component, mixed with plump amphophilic reactive fibroblasts and myofibroblasts morphologically similar to proliferative fasciitis. Immunohistochemistry was performed in 18 cases, showing focal positivity for smooth muscle actin (37.5%), desmin (40%), or both (14.3%), underlining the fibroblastic/myofibroblastic nature of these lesions, whereas S-100 and Pan-keratin were consistently negative. Follow-up data were available in 13 cases and ranged between 6 and 72 months (median: 31.3 mo); local recurrence was observed in 1 case in which the patient was physically debilitated. Recognition of this distinct entity as a reactive process, by no means always associated with debilitation, is essential to avoid confusion with soft tissue sarcomas.


Long-term sleep disturbances in children: a cause of neuronal loss.
Short-term sleep loss is known to cause temporary difficulties in cognition, behaviour and health but the effects of persistent sleep deprivation on brain development have received little or no attention. Yet, severe sleep disorders that last for years are common in children especially when they have neurodevelopmental disabilities. There is increasing evidence that chronic sleep loss can lead to neuronal and cognitive loss in children although this is generally unrecognized by the medical profession and the public. Without the restorative functions of sleep due to total sleep deprivation, death is inevitable within a few weeks. Chronic sleep disturbances at any age deprive children of healthy environmental exposure which is a prerequisite for cognitive growth more so during critical developmental periods. Sleep loss adversely effects pineal melatonin production which causes disturbance of circadian physiology of cells, organs, neurochemicals, neuroprotective and other metabolic functions. Through various mechanisms sleep loss causes widespread deterioration of neuronal functions, memory and learning, gene expression, neurogenesis and numerous other changes which cause decline in cognition, behaviour and health. When these changes are long-standing, excessive cellular stress develops which may result in widespread neuronal loss. In this review, for the first time, recent research advances obtained from various fields of sleep medicine are integrated in order to show that untreated chronic sleep disorders may lead to impaired brain development, neuronal damage and permanent loss of developmental potentials. Further research is urgently needed because these findings have major implications for the treatment of sleep disorders.


The Use of a Non-Absorbable Membrane as an Occlusive Barrier for Alveolar Ridge Preservation: A One Year Follow-Up Prospective Cohort Study.
:The aims of this study were to obtain preliminary data and test the clinical efficacy of a novel nonporous dense-polytetrafluoroethylene (d-PTFE) membrane (permamem®, botiss) in alveolar ridge preservation (ARP) procedures with a flapless approach. A traumatic extraction was performed in the premolar maxillary area, and a d-PTFE membrane was used to seal the alveolar cavity: no biomaterial was used to graft the socket and the membrane was left intentionally exposed and stabilized with sutures. The membrane was removed after four weeks and dental implants were placed four months after the procedure. The primary outcome variables were defined as the dimensional changes in the ridge width and height after four months. A total of 15 patients were enrolled in this study. The mean width of the alveolar cavity was 8.9 ± 1.1 mm immediately after tooth extraction, while four months later a mean reduction of 1.75 mm was experienced. A mean vertical reduction of 0.9 ± 0.42 mm on the buccal aspect and 0.6 ± 0.23 mm on the palatal aspect were recorded at implant placement. Within the limitations of this study, the d-PTFE membrane proved to be effective in alveolar ridge preservation, with the outcomes of the regeneration not affected by the complete exposure of this biomaterial.


The role of alkaline phosphatase in osteogenesis.
The role of alkaline phosphatase in osteogenesis has been investigated by histochemical techniques with particular attention to its relationship to phosphate metabolism and matrix elaboration. The upper tibial epiphysis mainly, and other epiphyses as well of growing rabbits, and the costochondral junctions of newborn human beings were studied, as were bone grafts in growing rabbits. The findings in the newborn human beings were identical with those in the rabbits. Phosphatase activity and free phosphate localization do not universally coincide. The enzyme appears to be intimately related to preosseous cellular metabolism and to the elaboration of a bone matrix that is chemically calcifiable. It remains possible, however, that phosphatase may be in some way involved in making inorganic salts available to the calcifiable matrix. If this function does exist it is a secondary one, since the elaboration of bone matrix, which is always associated with phosphatase activity, can and does occur in the absence of calcification. Calcification may occur later, in the absence of the enzyme. There is evidence to suggest that cartilage matrix is utilized in the formation of bone matrix. Phosphatase is physiologically active only in the presence of living cells. Where it is demonstrable in the absence of living cells, as in the cartilage remnants of the metaphysis, it appears to be physiologically inactive. Since phosphatase is temporarily inactivated in weakly acid media, and readily reactivated by alkaline solutions it is possible that the enzyme might survive in a physiologically inactive state in weakly acid tissues, and yet remain capable of histochemical demonstration in vitro in an alkaline medium. Phosphatase is not related to the disappearance of chondroitin sulfate.


Creativity and sensory gating indexed by the P50: selective versus leaky sensory gating in divergent thinkers and creative achievers.
Creativity has previously been linked with atypical attention, but it is not clear what aspects of attention, or what types of creativity are associated. Here we investigated specific neural markers of a very early form of attention, namely sensory gating, indexed by the P50 ERP, and how it relates to two measures of creativity: divergent thinking and real-world creative achievement. Data from 84 participants revealed that divergent thinking (assessed with the Torrance Test of Creative Thinking) was associated with selective sensory gating, whereas real-world creative achievement was associated with "leaky" sensory gating, both in zero-order correlations and when controlling for academic test scores in a regression. Thus both creativity measures related to sensory gating, but in opposite directions. Additionally, divergent thinking and real-world creative achievement did not interact in predicting P50 sensory gating, suggesting that these two creativity measures orthogonally relate to P50 sensory gating. Finally, the ERP effect was specific to the P50 - neither divergent thinking nor creative achievement were related to later components, such as the N100 and P200. Overall results suggest that leaky sensory gating may help people integrate ideas that are outside of focus of attention, leading to creativity in the real world; whereas divergent thinking, measured by divergent thinking tests which emphasize numerous responses within a limited time, may require selective sensory processing more than previously thought.


Biotechnologically produced secondary plant metabolites for cancer treatment and prevention.
Secondary metabolites of higher plants exert numerous effects on tumorigenesis, on tumor cells in vitro, tumors in experimental animals in vivo, interact with anti-cancer drugs, thus affecting positively or negatively their efficacy, and protect normal tissues of the host organism against adverse effects of anti-cancer therapies. The industrial development of pharmaceutical and nutraceutical products based on secondary plant metabolites is limited due to the following: (i) limited availability of their natural sources, (ii) concern about rare extinguishing plants, (iii) unavoidable contamination of plant extracts with environmental pollutants, (iv) seasonal variations in plant harvesting, (v) poor standardization of the final product due to variable conditions for plant growth, and (vi) difficulties of secondary metabolite extraction from the parts of grown plant. There is now steadily growing interest in the biotechnological approach to produce secondary metabolites using plant cell or plant tissue cultures. In the present review, biosynthesis of secondary metabolites and their role(s) in plant physiology will be briefly discussed; the biotechnological approach to active substances production in the plant cell and plant tissue cultures will be described; examples and mechanisms of cancer preventive and anti-cancer action of some biotechnologically produced plant metabolites will be provided; and future perspectives for biotechnologically produced plant-derived substances in the combined protocols for cancer treatment will be suggested.


Molecular interaction between natural IgG and ficolin--mechanistic insights on adaptive-innate immune crosstalk.
Recently, we found that natural IgG (nIgG; a non-specific immunoglobulin of adaptive immunity) is not quiescent, but plays a crucial role in immediate immune defense by collaborating with ficolin (an innate immune protein). However, how the nIgG and ficolin interplay and what factors control the complex formation during infection is unknown. Here, we found that mild acidosis and hypocalcaemia induced by infection- inflammation condition increased the nIgG:ficolin complex formation. Hydrogen-deuterium exchange mass spectrometry delineated the binding interfaces to the CH2-CH3 region of nIgG Fc and P-subdomain of ficolin FBG domain. Infection condition exposes novel binding sites. Site-directed mutagenesis and surface plasmon resonance analyses of peptides, derived from nIgG and ficolin, defined the interacting residues between the proteins. These results provide mechanistic insights on the interaction between two molecules representing the adaptive and innate immune pathways, prompting potential development of immunomodulatory/prophylactic peptides tunable to prevailing infection conditions.


Medical treatment as an alternative to adrenalectomy in patients with aldosterone-producing adenomas.
Primary aldosteronism (PA) and, in particular, its two commonest subtypes (i.e. idiopathic hyperaldosteronism (IHA) and aldosterone-producing adenoma (APA)) have been recognized as the most common cause of secondary hypertension. While 'conservative' medical treatment with aldosterone receptor antagonists is the therapeutic approach of choice in controlling blood pressure in patients with PA due to IHA, the more invasive (laparoscopic) adrenalectomy seems to be the most suitable therapy for patients with APA. In this review, we focus on the medical approach for the management of APA in cases where surgical excision of the adrenal is not possible.


Telomere attrition and growth: a life-history framework and case study in common terns.
The relationship between growth and age-specific telomere length, as a proxy of somatic state, is increasingly investigated, but observed patterns vary and a predictive framework is lacking. We outline expectations based on the assumption that telomere maintenance is costly and argue that individual heterogeneity in resource acquisition is predicted to lead to positive covariance between growth and telomere length. However, canalization of resource allocation to the trait with a larger effect on fitness, rendering that trait relatively invariant, can cause the absence of covariance. In a case study of common tern (Sterna hirundo) chicks, in which hatching order is the main determinant of variation in resource acquisition within broods, we find that body mass, but not telomere length or attrition, varies with hatching order. Moreover, body mass and growth positively predict survival to fledging, whereas telomere length and attrition do not. Using a novel statistical method to quantify standardized variance in plasticity, we estimate between-individual variation in telomere attrition to be only 12% of that of growth. Consistent with the relative invariance of telomere attrition, we find no correlation between age-specific body mass or growth and telomere attrition. We suggest that common tern chicks prioritize investment in long-term somatic state (as indicated by canalization of telomere maintenance) over immediate survival benefits of growth as part of an efficient brood reduction strategy that benefits the parents. As such, interspecific variation in the growth-telomere length relationship may be explained by the extent to which parents benefit from rapid mortality of excess offspring.


Prevalence and mortality in children with congenital diaphragmatic hernia: a multicountry study.
This study determined the prevalence, mortality, and time trends of children with congenital diaphragmatic hernia (CDH). Twenty-five hospital- and population-based surveillance programs in 19 International Clearinghouse for Birth Defects Surveillance and Research member countries provided birth defects mortality data between 1974 and 2015. CDH cases included live births, stillbirths, or elective termination of pregnancy for fetal anomalies. Prevalence, cumulative mortality rates, and 95% confidence intervals (CIs) were calculated using Poisson regression and a Kaplan-Meier product-limit method. Joinpoint regression analyses were conducted to assess time trends. The prevalence of CDH was 2.6 per 10,000 total births (95% CI: 2.5-2.7), slightly increasing between 2001 and 2012 (average annual percent change = 0.5%; 95% CI:-0.6 to 1.6). The total percent mortality of CDH was 37.7%, with hospital-based registries having more deaths among live births than population-based registries (45.1% vs. 33.8%). Mortality rates decreased over time (average annual percent change = -2.4%; 95% CI: -3.8 to 1.1). Most deaths due to CDH occurred among 2- to 6-day-old infants for both registry types (36.3%, hospital-based; 12.1%, population-based). The mortality of CDH has decreased over time. Mortality remains high during the first week and varied by registry type.


Schizophrenia and autism considered as the products of an agnosic right shift gene.
Crow (1995a) has argued that schizophrenia is caused by a gene associated with the evolution of human language and cerebral specialisation. This paper suggests a mechanism for Crow's theory which requires only one new assumption for the right shift genetic model of handedness and cerebral dominance (Annett, 1978). The proposal is that the RS+ allele, whose normal function is to induce the left hemisphere to serve speech by impairing speech-related cortex in the right hemisphere, tends to lose its directional coding. It becomes agnosic (RS+ a) for right versus left and impairs the left or right hemisphere at random. Schizophrenia is likely to develop when the RS+ a gene is paired with a normal RS+ gene but only in the 50% of cases where both hemispheres are affected. In the 50% where RS+ a affects the right hemisphere, development is normal as in the RS+ RS+ genotype. The risks for schizophrenia in monozygotic and dizygotic twins and other relatives are as expected for 50% expression of a Mendelian gene which is paired with a particular allele, but not alternative alleles at the same locus. The frequency of homozygotes for the agnosic gene is about 4 in 10,000, the rate observed for autism. A random pattern of double hemisphere deficits would give scope for a range of developmental strengths and weaknesses as observed within the spectrum of autistic disorders. Tests of the model require brain-imaging studies sensitive to individual differences in hemisphere lateralisation and a search for a genetic locus with human and nonhuman primate alleles, together with a mutant of the human form with a frequency of about 2%.


Formation of a noncovalent serpin-proteinase complex involves no conformational change in the serpin. Use of 1H-15N HSQC NMR as a sensitive nonperturbing monitor of conformation.
A structural understanding of the nature and scope of serpin inhibition mechanisms has been limited by the inability so far to crystallize any serpin-proteinase complex. We describe here the application of [(1)H-(15)N]-HSQC NMR on uniformly and residue-selectively (15)N-labeled serpin alpha(1)-proteinase inhibitor (Pittsburgh variant with stabilizing mutations) to provide a nonperturbing and exquisitely sensitive means of probing the conformation of the serpin alone and in a noncovalent complex with inactive, serine 195-modified, bovine trypsin. The latter should be a good model both for the few examples of reversible serpin-proteinase complexes and for the initial Michaelis-like complex formed en route to irreversible covalent inhibition. Cleavage of the reactive center loop, with subsequent insertion into beta-sheet A, caused dramatic perturbation of most of the NMR cross-peaks. This was true for both the uniformly labeled and alanine-specifically labeled samples. The spectra of uniformly or leucine- or alanine-specifically labeled alpha(1)-proteinase inhibitor in noncovalent complex with unlabeled inactive trypsin gave almost no detectable chemical shift changes of cross-peaks, but some general increase in line width. Residue-specific assignments of the four alanines in the reactive center loop, at P12, P11, P9, and P4, allowed specific examination of the behavior of the reactive center loop. All four alanines showed higher mobility than the body of the serpin, consistent with a flexible reactive center loop, which remained flexible even in the noncovalent complex with proteinase. The three alanines near the hinge point for insertion showed almost no chemical shift perturbation upon noncovalent complex formation, while the alanine at P4 was perturbed, presumably by interaction with the active site of bound trypsin. Reporters from both the body of the serpin and the reactive center loop therefore indicate that noncovalent complex formation involves no conformational change in the body of the serpin and only minor perturbation of the reactive center loop in the region which contacts proteinase. Thus, despite the large size of serpin and serpin-proteinase complex, 45 and 69 kDa respectively, NMR provides a very sensitive means of probing serpin conformation and mobility, which should be applicable both to noncovalent and to covalent complexes with a range of different proteinases, and probably to other serpins.


Optimizing Perioperative Red Blood Cell Utilization and Wastage in Pediatric Craniofacial Surgery.
Utilization, wastage, and adverse consequences of assigning one full red blood cell (RBC) unit were investigated for children undergoing craniosynostosis surgery. The authors hypothesized that significant RBC wastage in the perioperative period exists for pediatric craniofacial surgery. The authors sought to determine what factors could guide patient-specific blood product preparation by evaluating utilization and wastage of RBCs in pediatric patients undergoing surgical correction of craniosynostosis. Eighty-five children with craniosynostosis undergoing surgical correction at our institution between July 2013 and June 2015 were identified. Fifty-three patients received RBC transfusion in the perioperative period, while 32 patients were not transfused. Primary outcome measures were intraoperative, postoperative, and total percent of RBC wastage. Secondary analysis compared the impact of patient weight and procedure type on perioperative RBC wastage. Of the 53 patients who received perioperative RBC transfusion, 35 patients received a volume of blood less than the full volume of the RBC unit while 18 patients received the full volume of blood. There was no significant relationship between perioperative RBC wastage, the type of craniofacial procedure performed, or the duration of surgical time. Children who received a perioperative transfusion and had RBC wastage weighed significantly less than those who received a full volume. These findings suggest that for craniofacial surgical patients weighing less than 10 kg, a protocol that splits cross-matched RBC units can decrease perioperative RBC wastage and blood donor exposure. A future prospective study will determine the success of this intervention as well as the potential to decrease exposure to multiple blood donors.


Pilot simulation-based research for evaluation, training and assessment of holistic nursing at four intensive care unit sites.
This article was migrated. The article was marked as recommended. Background: Holistic nursing of intensive care unit (ICU) patients encompasses diverse challenges requiring regular in situ evaluation, training and assessment. Simulation has been adopted as a research and training tool in medicine; however, evidence for its use in enhancing holistic care at multi-sites is limited. Objective: This study aims to conduct a simulation-based research (SBR) at four ICU for standardized training of holistic nursing. Methods: There are stages of evaluating, training+in-training assessment and post-course assessment in this SBR. Specifically, the curriculum-mapped scenarios were developed according to the deficiency of each site after evaluating stage. At the training stage, the first simulation by team was defined as preparation step and the in-training assessment was undertaken at the second simulation. Results: From January 2017 to October 2018, sixty-four ICU nurses (16 teams, 4 teams in each site) at RCU, PICU, NICU and GYN ICU, attend 8 similar courses (2 courses at each site) over 20 months. In comparison with baseline performance, in-training assessments revealed the significant improvement of attendee's skills of holistic nursing. Attendees commented that simulation was a valuable training modality to enhance skills of holistic care including history taking, physical examination, communication and teamwork that are rarely taught among ICU nurses. Post-course workplace assessment by senior nurses revealed the high frequency of clinical application of holistic nursing by attendees. Additionally, post-course self assessment revealed a high attendee's confidence of holistic approaching in ICU. Conclusion: This pilot SBR demonstrated the feasibility of a standardized holistic care simulation program across four ICUs. In situ simulation and post-course workplace assessment affords situational learning without compromising patient safety and is an exciting and novel training of holistic nursing for ICU that could be integrated into regular intervention.


Lower urinary tract symptoms in young-middle aged males with a diagnosis of obstructive sleep apnea syndrome.
The aim of the current study is to measure the prevalence and the potential role of International Prostate Symptom Score (IPSS) score as a predictor of obstructive sleep apnea syndrome (OSAS) in male experienced lower urinary tract symptoms (LUTS). A cross-sectional web-based Italian survey was administered via Google Forms between July 17 and October 31, 2022. The urinary functioning was measured through the IPSS questionnaire. Specifically, we considered symptoms occurring more than "about half the time" (score ≥ 3) as bothering symptoms. Multivariable logistic regression models (LRMs) adjusting for age, body mass index (BMI), International Index of Erectile Function-5, IPSS, and hypertension were fitted to predict OSAS in the cohort of men responding to the survey and experiencing LUTS. Overall, 58 (24.4%) patients had a confirmed diagnosis of OSAS. The overall median IPSS was 5 (inter quartile range [IQR]: 3-8), respectively. According to IPSS items, 24 (10%), 44 (18.4%), 12 (5%), 12 (5%), 12 (5%), 11 (4.6%), 63 (26.4%) patients exhibit incomplete bladder emptying, urinary frequency, intermittency, urgency, weak stream, straining, nocturia with a score ≥ 3, respectively. After multivariable LRMs predicting the developing OSAS, age (odds ratio [OR]: 1.09, p < 0.001), BMI (OR:1.12, p < 0.001) and IPSS total score (OR:1.08, p = 0.02) were independent predicting factors. This analysis revealed that the IPSS total score, age, and BMI are independent predictors of OSAS in males. In this context, the use of IPSS in daily practice could be helpful in assessing the LUTS presence and in supporting physicians to identify a hidden sleep apnea condition.


Lethal and Sublethal Effects of Mineral Oil on Potato Pests.
Mineral oil is a product used to reduce Potato Virus Y transmission in potato fields. However, there is little information available about other effects that oil may have on insect pests of potato. To better understand how mineral oil affects potato pests, we performed a series of experiments testing the effects of oil on mortality, behavior, and development of potato aphids, Macrosiphum euphorbiae (Thomas) (Hemiptera: Aphididae), green peach aphids, Myzus persicae (Sulzer) (Hemiptera: Aphididae), and Colorado potato beetles, Leptinotarsa decemlineata (Say) (Coleoptera: Chrysomelidae). All three species showed negative behavioral responses to oil-treated potato foliage. Oil treatment also increased aphid mortality. Colorado potato beetle mortality was not affected, but developing on oil-treated potato plants resulted in prolonged development and smaller adults. Additionally, oil acted synergistically with the entomopathogenic fungus Beauveria bassiana (Balsamo) Vuillemin (Hypocreales: Clavicipitaceae); Colorado potato beetle larvae were killed more rapidly when sprayed with both products compared with when sprayed with B. bassiana alone. Based on these results, mineral oil has the potential for expanded use in potato IPM programs.


Inclusion of immigrant status in smoking prevalence statistics.
Data from the 1995-1996 and 1998-1999 Current Population Survey tobacco use supplements were used to examine smoking prevalence statistics by race/ethnicity and immigrant status. Smoking prevalence statistics were calculated, and these data were decomposed by country of birth for Asian immigrants to illustrate the heterogeneity in smoking rates present within racial/ethnic groups. Except in the case of male Asian/Pacific Islanders, immigrants exhibited significantly lower smoking prevalence rates than nonimmigrants. However, rates varied according to country of birth. This research highlights the need to disaggregate health statistics by race/ethnicity, sex, immigrant status, and, among immigrants, country of birth. Data on immigrants' health behaviors enhance the development of targeted and culturally sensitive public health smoking prevention programs.


The competition between endogenous dopamine and radioligands for specific binding to dopamine receptors.
The ternary complex model of G-protein-linkage to receptors holds that agonists increase the affinity of the receptors for the G protein. Consequently, an agonist can exert the greatest inhibition of the binding of radioligands which are also agonists. We hypothesized that competition from endogenous dopamine in striatum of living mice should thus have a greater effect on the binding of the D(2,3) agonist N-[(3)H]propylnorapomorphine ([(3)H]NPA), than on the binding of the D(2,3) antagonist [(11)C]raclopride in living brain. The binding potential (p(B(0))), defined as the ratio of bound-to-unbound ligand after reserpine treatment, was measured in mouse striatum for [(11)C]raclopride (p(B(0))(RAC)(C)) = 8.5, and for [(3)H]NPA(p(B(0))(NPA)) = 5.3. Relative to these baseline values after dopamine depletion, saline-treatment decreased the p(B) of [(3)H]NPA by one-half, while the p(B) of [(11)C]raclopride declined by only one-third. Amphetamine decreased the p(B) of [(3)H]NPA to a greater extent than that of [(11)C]raclopride. The apparent inhibition constant of endogenous dopamine depended on the dopamine occupancy and declined to a value 1.66 times greater for [(3)H]NPA than for [(11)C]raclopride at its highest occupancies. Thus, the agonist binding was more sensitive than antagonist binding to competition from endogenous dopamine. Dopamine agonist ligands may be especially useful for PET studies of dopamine receptor occupancy by endogenous synaptic dopamine. Analysis of the effect of dopamine occupancy on the inhibition of agonist indicated a limited supply of G protein, with a maximum ternary complex fraction of 40% of maximum antagonist binding capacity.


Impact of cardiorespiratory fitness on the obesity paradox in patients with heart failure.
To determine the impact of cardiorespiratory fitness (FIT) on survival in relation to the obesity paradox in patients with systolic heart failure (HF). We studied 2066 patients with systolic HF (body mass index [BMI] ≥18.5 kg/m(2)) between April 1, 1993 and May 11, 2011 (with 1784 [86%] tested after January 31, 2000) from a multicenter cardiopulmonary exercise testing database who were followed for up to 5 years (mean ± SD, 25.0±17.5 months) to determine the impact of FIT (peak oxygen consumption <14 vs ≥14 mL O2 ∙ kg(-1) ∙ min(-1)) on the obesity paradox. There were 212 deaths during follow-up (annual mortality, 4.5%). In patients with low FIT, annual mortality was 8.2% compared with 2.8% in those with high FIT (P<.001). After adjusting for age and sex, BMI was a significant predictor of survival in the low FIT subgroup when expressed as a continuous (P=.03) and dichotomous (<25.0 vs ≥25.0 kg/m(2)) (P=.01) variable. Continuous and dichotomous BMI expressions were not significant predictors of survival in the overall and high FIT groups after adjusting for age and sex. In patients with low FIT, progressively worse survival was noted with BMI of 30.0 or greater, 25.0 to 29.9, and 18.5 to 24.9 (log-rank, 11.7; P=.003), whereas there was no obesity paradox noted in those with high FIT (log-rank, 1.72; P=.42). These results indicate that FIT modifies the relationship between BMI and survival. Thus, assessing the obesity paradox in systolic HF may be misleading unless FIT is considered.


Drosophila MOF controls Checkpoint protein2 and regulates genomic stability during early embryogenesis.
In Drosophila embryos, checkpoints maintain genome stability by delaying cell cycle progression that allows time for damage repair or to complete DNA synthesis. Drosophila MOF, a member of MYST histone acetyl transferase is an essential component of male X hyperactivation process. Until recently its involvement in G2/M cell cycle arrest and defects in ionizing radiation induced DNA damage pathways was not well established. Drosophila MOF is highly expressed during early embryogenesis. In the present study we show that haplo-insufficiency of maternal MOF leads to spontaneous mitotic defects like mitotic asynchrony, mitotic catastrophe and chromatid bridges in the syncytial embryos. Such abnormal nuclei are eliminated and digested in the yolk tissues by nuclear fall out mechanism. MOF negatively regulates Drosophila checkpoint kinase 2 tumor suppressor homologue. In response to DNA damage the checkpoint gene Chk2 (Drosophila mnk) is activated in the mof mutants, there by causing centrosomal inactivation suggesting its role in response to genotoxic stress. A drastic decrease in the fall out nuclei in the syncytial embryos derived from mof¹/+; mnkp⁶/+ females further confirms the role of DNA damage response gene Chk2 to ensure the removal of abnormal nuclei from the embryonic precursor pool and maintain genome stability. The fact that mof mutants undergo DNA damage has been further elucidated by the increased number of single and double stranded DNA breaks. mof mutants exhibited genomic instability as evidenced by the occurance of frequent mitotic bridges in anaphase, asynchronous nuclear divisions, disruption of cytoskeleton, inactivation of centrosomes finally leading to DNA damage. Our findings are consistent to what has been reported earlier in mammals that; reduced levels of MOF resulted in increased genomic instability while total loss resulted in lethality. The study can be further extended using Drosophila as model system and carry out the interaction of MOF with the known components of the DNA damage pathway.


A Cross-Lagged Panel Analysis of Psychometric Intelligence and Achievement in Reading and Math.
A cross-lagged panel analysis of Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV) intelligence test scores and reading and math achievement test scores of 337 students twice assessed for special education eligibility across a test-retest interval of 2.85 years was conducted. General intelligence (g) was loaded by the four WISC-IV factor index scores whereas reading and math were composite scores. After confirming measurement invariance, it was found that g, reading, and math were stable across time and synchronously correlated. The cross-lagged paths from g at time 1 to reading and math at time 2 (0.26 and 0.39, respectively) were both significantly greater than zero whereas the paths from reading and math at time 1 to g at time 2 (0.03 and 0.23, respectively) were not statistically significant. Given this pattern of relationships and extant research on the correlates of general intelligence, it was tentatively inferred that general intelligence was the temporal precursor to reading and math achievement.


Lymphangioleiomyomatosis Biomarkers Linked to Lung Metastatic Potential and Cell Stemness.
Lymphangioleiomyomatosis (LAM) is a rare lung-metastasizing neoplasm caused by the proliferation of smooth muscle-like cells that commonly carry loss-of-function mutations in either the tuberous sclerosis complex 1 or 2 (TSC1 or TSC2) genes. While allosteric inhibition of the mechanistic target of rapamycin (mTOR) has shown substantial clinical benefit, complementary therapies are required to improve response and/or to treat specific patients. However, there is a lack of LAM biomarkers that could potentially be used to monitor the disease and to develop other targeted therapies. We hypothesized that the mediators of cancer metastasis to lung, particularly in breast cancer, also play a relevant role in LAM. Analyses across independent breast cancer datasets revealed associations between low TSC1/2 expression, altered mTOR complex 1 (mTORC1) pathway signaling, and metastasis to lung. Subsequently, immunohistochemical analyses of 23 LAM lesions revealed positivity in all cases for the lung metastasis mediators fascin 1 (FSCN1) and inhibitor of DNA binding 1 (ID1). Moreover, assessment of breast cancer stem or luminal progenitor cell biomarkers showed positivity in most LAM tissue for the aldehyde dehydrogenase 1 (ALDH1), integrin-ß3 (ITGB3/CD61), and/or the sex-determining region Y-box 9 (SOX9) proteins. The immunohistochemical analyses also provided evidence of heterogeneity between and within LAM cases. The analysis of Tsc2-deficient cells revealed relative over-expression of FSCN1 and ID1; however, Tsc2-deficient cells did not show higher sensitivity to ID1-based cancer inhibitors. Collectively, the results of this study reveal novel LAM biomarkers linked to breast cancer metastasis to lung and to cell stemness, which in turn might guide the assessment of additional or complementary therapeutic opportunities for LAM.


Consumer and carer perspectives in the development of a mental health research, treatment and teaching facility: A thematic analysis.
WHAT IS KNOWN ON THE SUBJECT?: Around the world, recovery has become a focus in mental health policy. The participation of people accessing mental health services (consumers) and carers of such individuals in decision-making related to services forms part of this recovery orientation and studies suggest positive outcomes following such participation. However, little is known about consumer and carer desires at the earliest stages of development of new services. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: Consumers and carers desire changes to how mental health services are provided. Many factors affect consumer and carer experiences, including language use, physical design of spaces, accessibility, consideration of individual needs, practical help and how well care is continued from hospital to community settings. Carers may feel sidelined in treatment and be distressed as a result. They wish to be respected and involved in recovery. Consumers and carers wish for focus on broader health, with care taken to address physical health, psychological needs, social needs and treatment of the whole person rather than just an illness. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Consumers and carers desire partnership with professionals in recovery. Tokenistic participation should be avoided. Flexibility in how services are provided and less formality may help engage consumers and carers. Specifically, professionals may help by linking consumers and carers to services that address practical needs. Professionals should communicate with carers to draw on their expertise about the individual accessing the mental health service and help carers understand how they can assist the individual's recovery. Introduction Recovery-oriented mental health policies recognize consumer and carer participation in service decision-making as essential, but little is known about the views of these individuals in the earliest stages of service development. Aim This study sought consumer and carer perspectives addressing the establishment of a mental health research, treatment and teaching facility in their region. Methods Two 2-hr focus groups were conducted, with separate groups held for mental health consumers (n = 9) and carers (n = 9), respectively. Discussions pertained to mental health literacy, gaps in current services, desires for an ideal facility (in terms of physical design and services offered) and what would help in recovery. Results Inductive thematic analysis was used to generate three themes: care outside of consultations, carer involvement in recovery and holistic approaches to mental health care. Consumers desired a facility that could cater to individual needs. Carers felt excluded in recovery and unable to provide effective support. Both groups preferred holistic approaches to mental health, expressing ambivalence towards medication and hospitalization. Discussion Consumers and carers have many needs that conventional practices may not meet. Implications for practice They have clear desires for equal partnership in recovery and for transformation of conventional treatment methods.


Efficacy of different treatment strategies for hepatocellular carcinoma with portal vein tumor thrombosis.
To evaluate the efficacy of different treatment strategies for hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) and investigate factors influencing prognosis. One hundred and seventy-nine HCC patients with macroscopic PVTT were enrolled in this study. They were divided into four groups and underwent different treatments: conservative treatment group (n = 18), chemotherapy group (n = 53), surgical resection group (n = 24) and surgical resection with postoperative chemotherapy group (n = 84). Survival rates of the patients were analyzed by the Kaplan-Meier method. A log-rank analysis was performed to identify group differences. Cox's proportional hazards model was used to analyze variables associated with survival. The mean survival periods of the patients in four groups were 3.6, 7.3, 10.1, and 15.1 mo respectively. There were significant differences in the survival rates among the groups. The survival rates at 0.5-, 1-, 2-, and 3-year in surgical resection with postoperative chemotherapy group were 55.8%, 39.3%, 30.4%, and 15.6% respectively, which were significantly higher than those of other groups (P<0.001). Multivariate analysis revealed that the strategy of treatment (P<0.001) and the number of chemotherapy cycles (P = 0.012) were independent survival predictors for patients with HCC and PVTT. Surgical resection of HCC and PVTT combined with postoperative chemotherapy or chemoembolization is the most effective therapeutic strategy for the patients who can tolerate operation. Multiple chemotherapeutic courses should be given postoperatively to the patients with good hepatic function reserve.


The zygotic control of Drosophila pair-rule gene expression. I. A search for new pair-rule regulatory loci.
The examination of pair-rule gene expression in wild-type and segmentation mutant embryos has identified many, but not necessarily all, of the elements of the regulatory system that establish their periodic patterns. Here we have conducted a new type of search for previously unknown regulators of these genes by examining pair-rule gene expression in blastoderm embryos lacking parts of or entire chromosomes. This method has the advantage of direct inspection of abnormal pair-rule gene patterns without relying upon mutagenesis or interpretation of larval phenotypes for the identification of segmentation genes. From these experiments we conclude that: (i) most zygotically required regulators of the fushi tarazu (ftz), even-skipped (eve) and hairy (h) pair-rule genes have been identified, except for one or more loci we have uncovered on chromosome arm 2L; (ii) the repression of the ftz and eve genes in the anterior third of the embryo is under maternal, not zygotic control; and (iii) there are no general zygotically required activators of pair-rule gene expression. The results suggest that the molecular basis of pair-rule gene regulation can be pursued with greater confidence now that most key trans-acting factors are already in hand.


Imaging of autism: lessons from the past to guide studies in the future.
To review the scientific literature on the imaging of autism with a view to understanding how imaging can contribute to future studies. Medline was searched, and bibliographies from retrieved articles were reviewed. Inclusion criteria were a diagnosis of autism according to Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria, third edition or later, and a control group without autism. The field suffers from a lack of replication studies and poor methodology in terms of not controlling for confounding variables. Enlarged brain size, particularly in the temporoparietal brain region, and decreased size of the posterior corpus callosum are the only findings that have been independently replicated. Future imaging studies should attempt to investigate more homogeneous subgroups of patients such as those with "the lesser variant of PDD" and high-functioning patients with PDD who do not have comorbid medical conditions. A different approach, examining the individual behaviours that constitute the PDD spectrum and exploring these separately along with other associated variables such as neuropsychological deficits, structural and functional brain abnormalities, and genetic information could help identify biological mechanisms that do not follow diagnostic boundaries.


Noise estimation in magnitude MR datasets.
Estimating the noise parameter in magnitude magnetic resonance (MR) images is important in a wide range of applications. We propose an automatic noise estimation method that does not rely on a substantial proportion of voxels being from the background. Specifically, we model the magnitude of the observed signal as a mixture of Rice distributions with common noise parameter. The expectation-maximization (EM) algorithm is used to estimate all parameters, including the common noise parameter. The algorithm needs initializing values for which we provide some strategies that work well. The number of components in the mixture model also needs to be estimated en route to noise estimation and we provide a novel approach to doing so. Our methodology performs very well on a range of simulation experiments and physical phantom data. Finally, the methodology is demonstrated on four clinical datasets.


Light-emitting diode therapy (LEDT) before matches prevents increase in creatine kinase with a light dose response in volleyball players.
Low-level laser (light) therapy (LLLT) has been applied over skeletal muscles before intense exercise (muscular pre-conditioning) in order to reduce fatigue and muscle damage (measured by creatine kinase, CK) in clinical trials. However, previous exercise protocols do not exactly simulate the real muscle demand required in sports. For this reason, the aim of this randomized and double-blind placebo-controlled trial was to investigate whether light-emitting diode therapy (LEDT) applied over the quadriceps femoris muscles, hamstrings, and triceps surae of volleyball players before official matches could prevent muscle damage (CK) with a dose response, establishing a therapeutic window. A professional male volleyball team (12 athletes) was enrolled in this study, and LEDT was applied before 4 matches during a national championship. LEDT used an array of 200 light-emitting diodes (LEDs) arranged in 25 clusters of 4 infrared LEDs (850 ± 20 nm; 130 mW) and 25 clusters of 4 red LEDs (630 ± 10 nm; 80 mW). Athletes were randomized to receive one of four different total doses over each muscle group in a double-blind protocol: 105 J (20 s), 210 J (40 s), 315 J (60 s), and placebo (no light for 30 s). CK in blood was assessed 1 h before and 24 h after each match. LEDT at 210 J avoided significant increases in CK (+10 %; P = 0.993) as well as 315 J (+31 %, P = 0.407). Placebo (0 J) allowed a significant increase in CK (+53 %; P = 0.012) as well as LEDT at 105 J (+59 %; P = 0.001). LEDT prevented significant increases of CK in blood in athletes when applied before official matches with a light dose response of 210-315 J, suggesting athletes might consider applying LEDT before competition.


Metabolic outcome during 1 year in newly detected hypertensives: results of the Antihypertensive Treatment and Lipid Profile in a North of Sweden Efficacy Evaluation (ALPINE study).
The aim of the Antihypertensive Treatment and Lipid Profile in a North of Sweden Efficacy Evaluation study was to compare the long-term effect of the commonly used inexpensive medication with a low-dose diuretic (hydrochlorothiazide), alone or in combination with a beta-adrenoceptor (atenolol), with that of more modern but also more expensive antihypertensive treatment with an angiotensin-II-receptor blocker (candesartan), alone or in combination with a calcium antagonist (felodipine), and to do so in newly diagnosed patients with primary hypertension. The objectives included comparisons of the effects on the glucose metabolism, lipoprotein metabolism, electrolytes, blood pressure, and subjective symptoms. A 1-year, prospective randomized, double-blind, controlled trial. In an investigator-initiated study, we included 392 patients (mean age 55 years, 48% men); 370 patients (94%) had never been treated with antihypertensive drugs before the study. No patient was lost to follow-up. Both treatment regimens lowered blood pressure well (23/13 mmHg in the hydrochlorothiazide group and 21/13 mmHg in the candesartan group), with a majority of patients needing two drugs. Fasting levels of both serum insulin and plasma glucose increased in the hydrochlorothiazide group in contrast to unaffected levels in the candesartan group. Diabetes mellitus was diagnosed in nine patients during follow-up, in eight patients in the hydrochlorothiazide group (4.1%) and in one patient (0.5%) in the candesartan group (P = 0.030). Triglycerides increased and high-density lipoprotein-cholesterol decreased more in the hydrochlorothiazide group than in the candesartan group. Both the low-density lipoprotein/high-density lipoprotein and the apolipoprotein B/apolipoprotein A-I ratios increased in the hydrochlorothiazide group. At 12 months, 18 patients in the hydrochlorothiazide group versus five in the candesartan group had a 'metabolic syndrome', as defined by the World Health Organization (P = 0.007) despite 1 year of active blood pressure-lowering therapy. There were less (P = 0.020) adverse events in the candesartan group, but no major differences in the subjective symptoms assessment profile. One subject in each group had a myocardial infarction. Antihypertensive treatment with a diuretic, if needed combined with a beta-adrenoceptor blocker, was associated with an aggravated metabolic profile; this was not so for patients treated with an angiotensin-II-receptor blocker, if needed combined with a calcium antagonist. An antihypertensive treatment strategy that costs more in the short run but has no metabolic adverse effects may have a health economic impact in the long term.


Cholesterol granuloma in thyroglossal cysts: a clinicopathological study.
Thyroglossal duct cyst (TDC) is a congenital anomaly caused by retention of epithelial remnants from the descent of the thyroid gland during embryological development. Cholesterol granuloma represents a granulomatous reaction to precipitates of cholesterol crystals in tissue, usually related to middle-ear disease. The association of TDC with cholesterol granuloma has hardly been reported. This study describes five patients with TDC and cholesterol granuloma over a 16-year-period. The treatment consisted of excision of the TDC and the mid-portion of the hyoid bone and excision of a core of tissue between the hyoid bone and the foramen cecum (Sistrunk procedure). We speculate that the pathogenesis of cholesterol granuloma in TDC resembles that in the paranasal sinuses, as both sites provide a closed, poorly ventilated hollow structure with slow drainage. Our five patients accounted for 13% of all patients with TDC treated in our center during the same period, indicating that cholesterol granuloma in TDC may not be as rare as previously thought.


Isolation and Quantification of Methylated Cell-Free DNA in Plasma on an Integrated Microfluidic System.
Methylated cell-free DNA (cfDNA) has been deemed a promising biomarker for ovarian cancer (OvCa) prognosis and therapy selection. However, exploring the methylation profiles of tumor suppressor genes in cfDNA remains a challenge due to their extremely low concentrations and complicated protocols, as well as methodological constraints. In this study, an integrated microfluidic system was developed to automatically (1) capture methylated cfDNA in plasma by magnetic beads coated with the methyl-CpG-binding domain and (2) quantify the methylation level of tumor suppressor genes by on-chip quantitative polymerase chain reaction (qPCR). For capturing methylated cfDNA from a very small amount of plasma, samples along with beads were mixed in a new micromixer to enhance the capture rate. With a high capture rate (72%) and a limit of quantification of 0.1 pg/μL (3 orders of magnitude lower than that of the benchtop method), the compact system could detect the methylated cfDNA from only 20 μL of plasma sample in 2 h. Furthermore, the dynamic range, from 0.1 to 2000 pg/μL of methylated cfDNA, spans the physiological range in plasma, signifying that this device has great potential for personalized medicine in OvCa.


Limited efficacy of early postoperative jejunal feeding.
Twenty patients underwent placement of a jejunal catheter for early postoperative feeding at the time of upper abdominal operations, and a control group of 11 patients underwent operative procedures of similar magnitude without jejunostomy. Advancement of the rate of feeding to target intake over 6 to 7 days was attempted. Complications from the feeding led to cessation or curtailment of intake in 65 percent of the patients. Specific complications included abdominal pain and distention, diarrhea, and retrograde reflux of the feeding into the stomach. No statistically significant difference in nitrogen balance was demonstrated between the fed and unfed groups, presumably due to the limitations of nutrient delivery or absorption in the fed groups or elevated breath hydrogen excretion in patients with abdominal pain and distention suggests that the nature of the nutrients, particularly complex carbohydrates, is a factor in the development of feeding complications. Caution must be exercised in advancing the rate of postoperative jejunal feeding.


A Novel Way to Secure the Laryngeal Mask Airway During Oral Surgery Procedures.
The laryngeal mask airway (LMA) has been used successfully for an ever-increasing number of applications. Utilization in oral maxillofacial surgery has been hampered by surgical difficulties working around the device. In this case series, a novel device, the LMA-PROP, was used to determine whether it was possible to alleviate device-positioning concerns with third molar extraction cases. LMA-PROP was used with both anesthesia and surgical satisfaction in this small pilot study. LMA-PROP appears to be a helpful new tool allowing the surgeon to maintain current surgical techniques for third molar extraction while securing LMA adequately for anesthesia maintenance.


Prevalence of sleep-disordered breathing in an African general population: The Benin Society and Sleep (BeSAS) study.
Data on the prevalence of sleep-disordered breathing (SDB) in the African general population are scarce, and a better understanding is urgently needed. Our study aimed to objectively determine the prevalence of, and factors associated with, SDB in a large sample in Benin, west Africa. In the Benin Society and Sleep (BeSAS) cross-sectional study, participants aged 25 years and older were recruited from both urban and rural areas. Rural participants were recruited from Tanve, a village located 200 km north of Cotonou, and urban participants were recruited from Cotonou. The participants underwent respiratory polygraphy at home using a type-3 device that measures airflow through a nasal pressure sensor, respiratory effort (thoracic movement), and pulse oximetry. Clinical and morphometric data were also collected. SDB severity categories were defined according to the apnoea-hypopnoea index (AHI), with mild-to-severe SDB (AHI ≥5/h), moderate-to-severe SDB (AHI ≥15/h), and severe SDB (AHI ≥30/h). The study was completed from April 4, 2018 to Jan 15, 2021. Of 2909 participants recruited in the BeSAS study, 2168 (74·5%) underwent respiratory polygraphy. For the 1810 participants with complete polygraphic data (mean age 46 years, SD 15; 1163 [64·2%] women), the prevalence of mild-to-severe SDB (AHI ≥5/h) was 43·2% (95% CI 40·9-45·5), of moderate-to-severe SDB (AHI ≥15/h) was 11·6% (10·2-13·1), and of severe SDB (AHI ≥30/h) was 2·7% (2·0-3·5). Factors independently associated with SDB were advanced age, male sex, large neck circumference, abdominal obesity, overweight or obesity, and snoring. After multivariable adjustment, severe SDB was independently associated with hypertension in women (odds ratio 3·99, 95% CI 1·04-15·33; ptrend=0·044), but not in men (odds ratio 0·67, 0·22-2·05; Ptrend=0·63). The BeSAS study provides the first large-scale objective evaluation of SDB prevalence and associated factors in Africa. The high prevalence of SDB identified should stimulate the development of public health policies to prevent and treat this condition in African countries. Ligue Pulmonaire Vaudoise, Switzerland.


Interferon in the management of neuroendocrine GEP-tumors: a review.
Interferon has been known to be an effective antiviral and antitumor agent since the 1960s. However, a large majority of solid tumors did not respond to this kind of treatment. In early 1980s, alpha interferon was introduced in the management of classical midgut carcinoids with promising results. Since then, more than 500 patients have been treated with alpha interferon worldwide and published in the literature. The median dose has been 5 million units 3-5 times per week subcutaneously. The subjective response rate is about 60%, biochemical responses in 44% and tumor responses in 11% of the patients. There are very few randomized control trials at the moment which make survival analysis difficult but in different centers median survivals from start of treatment in malignant midgut carcinoids has been reported to be more than 3 years. The mechanisms of action of alpha interferon are direct effects on the tumor cells by inhibiting the cell proliferation via cell cycle block G1-S phase. Induction of interferon inducable genes, such as p-21, p-27, 2-5-A-synthetase, PKR, IRF-1, IRF-2. All these contribute to reduction of the growth potential of the tumor. Furthermore, alpha interferon exerts an immunomodulatory effect stimulating natural killer cells, macrophages and also presents anti-angiogenetic effects. In the future, long-acting formulations of recombinant alpha interferons will come into clinical use, such as polyethylene glycosylated interferons. It will facilitate the treatment for the patients and also perhaps reduce the side effects, which are sometimes significant during treatment with alpha interferon. It might also be possible to give higher doses of alpha interferon with hopefully improved clinical efficacy.


Prodromal angina is associated with myocardial salvage in acute ST-segment elevation myocardial infarction.
Previous studies have shown that prodromal angina (PA) occurs frequently in acute myocardial infarction (MI) patients. However, the potential benefits of PA on ischaemic myocardial damage remain unknown. One-hundred and fifty-four patients with acute ST-segment elevation MI successfully treated with primary percutaneous coronary intervention (PPCI) were prospectively evaluated for new-onset PA in the week preceding infarction and other factors known to influence myocardial salvage. Cardiovascular magnetic resonance was performed 8 ± 3 days after MI for the assessment of area-at-risk (AAR), MI size, myocardial haemorrhage (MH), microvascular obstruction (MO), and myocardial salvage index (MSI). Patients with PA (n = 60) compared with those without PA (n = 94) showed similar AAR but significantly smaller MI size leading to larger MSI (0.53 ± 0.27 vs. 0.32 ± 0.26, P < 0.001). Additionally, patients with PA had lower incidence of MH (18 vs. 33%) and MO (22 vs. 46%) than non-PA patients (both P < 0.05). At univariate analysis, higher MSI was associated with new-onset PA, lower myocardial oxygen consumption before PPCI, shorter time-to-PPCI, and higher post-procedural TIMI flow-grade. Neither collateral circulation nor medications administered before PPCI were associated to MSI. After correction for other covariates by multivariate analysis, new-onset PA remained significantly associated with MSI (β-value: 0.352, P < 0.001). In acute MI patients, new-onset PA is associated with higher MSI independent of others factors known to influence jeopardized myocardium, as well as with less microvascular damage.


Hepatic expression of macrophage inflammatory protein-1 alpha and macrophage inflammatory protein-1 beta after liver transplantation.
Two local events that are crucial for T cell emigration into tissue are (1) activation of T cell integrins to permit binding to endothelial counter-receptors and (2) directed migration through the endothelium and into tissue in response to chemotactic factors. Because the chemokines macrophage inflammatory protein-1 alpha (MIP-1 alpha) and MIP-1 beta can activate adhesion and induce migration of T cells in vitro, we investigated their expression in human liver allografts to determine whether they might be involved in regulating the recruitment of T cells to allografts in vivo. Both chemokines were expressed strongly by infiltrating leukocytes during rejection and could be detected immunohistochemically on biliary epithelium, an important target for T cell mediated graft damage. Both chemokines, but particularly MIP-1 beta, were detected on the vascular and sinusoidal endothelium of rejecting liver allografts, where they were coexpressed with the T cell beta 1-integrin receptor vascular cell adhesion molecule-1. In situ hybridization with complementary ribonucleic acid probes showed no MIP-1 alpha or MIP-1 beta mRNA in normal liver but dramatic expression of both chemokines in infiltrating leukocytes and graft endothelium during rejection. Expression was reduced after successful corticosteroid treatment of rejection but persisted in patients progressing to chronic rejection. Increased MIP-1 alpha and MIP-1 beta mRNA expression was already found in biopsies taken at the end of the transplant operation, suggesting that early induction of chemokines, possibly in response to graft reperfusion, might promote the subsequent development of graft rejection. These data demonstrate for the first time that MIP-1 alpha and MIP-1 beta are (1) expressed in human liver allografts, (2) produced by endothelial cells in vivo, and (3) induced early after transplantation. They suggest that MIP-1 alpha and MIP-1 beta produced by graft infiltrating leukocytes and graft endothelium might play a crucial role in regulating T cell recruitment to liver allografts in vivo.


Amino acid classification based spectrum kernel fusion for protein subnuclear localization.
Prediction of protein localization in subnuclear organelles is more challenging than general protein subcelluar localization. There are only three computational models for protein subnuclear localization thus far, to the best of our knowledge. Two models were based on protein primary sequence only. The first model assumed homogeneous amino acid substitution pattern across all protein sequence residue sites and used BLOSUM62 to encode k-mer of protein sequence. Ensemble of SVM based on different k-mers drew the final conclusion, achieving 50% overall accuracy. The simplified assumption did not exploit protein sequence profile and ignored the fact of heterogeneous amino acid substitution patterns across sites. The second model derived the PsePSSM feature representation from protein sequence by simply averaging the profile PSSM and combined the PseAA feature representation to construct a kNN ensemble classifier Nuc-PLoc, achieving 67.4% overall accuracy. The two models based on protein primary sequence only both achieved relatively poor predictive performance. The third model required that GO annotations be available, thus restricting the model's applicability. In this paper, we only use the amino acid information of protein sequence without any other information to design a widely-applicable model for protein subnuclear localization. We use K-spectrum kernel to exploit the contextual information around an amino acid and the conserved motif information. Besides expanding window size, we adopt various amino acid classification approaches to capture diverse aspects of amino acid physiochemical properties. Each amino acid classification generates a series of spectrum kernels based on different window size. Thus, (I) window expansion can capture more contextual information and cover size-varying motifs; (II) various amino acid classifications can exploit multi-aspect biological information from the protein sequence. Finally, we combine all the spectrum kernels by simple addition into one single kernel called SpectrumKernel+ for protein subnuclear localization. We conduct the performance evaluation experiments on two benchmark datasets: Lei and Nuc-PLoc. Experimental results show that SpectrumKernel+ achieves substantial performance improvement against the previous model Nuc-PLoc, with overall accuracy 83.47% against 67.4%; and 71.23% against 50% of Lei SVM Ensemble, against 66.50% of Lei GO SVM Ensemble. The method SpectrumKernel+ can exploit rich amino acid information of protein sequence by embedding into implicit size-varying motifs the multi-aspect amino acid physiochemical properties captured by amino acid classification approaches. The kernels derived from diverse amino acid classification approaches and different sizes of k-mer are summed together for data integration. Experiments show that the method SpectrumKernel+ significantly outperforms the existing models for protein subnuclear localization.


[Electromyograms in erectile dysfunction and computer-assisted interpretation].
The electromyogram of the corpora cavernosa (CC-EMG) provides information on the autonomic innervation and/or smooth musculature. The interpretation of the CC-EMG, usually by evaluating signal patterns of higher activity, is time-consuming. To improve this situation, a computer-aided diagnosis employing a Microsoft Windows user interface was developed. The computer-aided interpretation is based on digital measurement data obtained using a 170.6 Hz sampling frequency and quantization of 10 V/12 bits of the signal. The first task of the program is to extract signal patterns of higher activity from stored data. To describe these patterns in mathematical terms, the features "relative time position", "relative reproducibility", "portion of normal phases", and "portion of whip phases" are calculated. Characteristic signal forms (normal and whip phases) are identified by means of syntactic pattern recognition. Using fuzzy logic, the features are used to effect pattern evaluation. To summarize the evaluated patterns, the variable "global normality" has been established, and linked to the "global synchronicity" at a second fuzzy logic level, to produce the final diagnosis. Finally, 30 records were evaluated independently by a team of experts and by the computer program. In relation to four established diagnostic classes, a correspondence of 70% was found. Furthermore, the accuracy achieved in each of the individual classes was better than 50%. Discrimination between normal and abnormal evaluation, which is of particular interest, reached 80%.


CTRP3 modulates the expression and secretion of adipokines in 3T3-L1 adipocytes.
The objective of this study was to investigate the impact of C1q/TNF related protein 3 (CTRP3), a novel adipokine, on the expression and secretion of adiponectin, leptin, visfatin, and apelin in 3T3-L1 adipocytes. The effect of insulin resistance on the impact was also investigated. 3T3-L1 adipocytes were treated with different concentrations (0, 10, 50, 250, 1250 ng/mL) CTRP3 for 12 h, and with 250 ng/mL CTRP3 for different times (0, 6, 12, 24, 48 h). The expression of adipokines between normal and insulin resistant adipocytes, as well as between the adipocytes pre-treated with and without Compound C were compared. The secretion and gene expression of the adipokines were detected by enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (RT-PCR), respectively. The relative expression of AMPK (thr172) was detected by western blot analysis. With the increase in CTRP3 concentration or the duration of the treatment, the secretion of adiponectin, leptin, visfatin and apelin were all increased accordingly, which was significant under the treatment with 250 ng/mL and 1250 ng/mL CTRP3 for 12 h as well as 250 ng/mL CTRP3 for 12 h, 24 h and 48 h. Gene expression showed a similar trend. The secretion and gene expression of adipokines in insulin resistant adipocytes were all decreased significantly in comparison with that of normal adipocytes. The secretion secretion and gene expression of adiponectin, and the relative expression of AMPK (thr172) in adipocytes pre-treated with Compound C were decreased significantly in comparison with that in adipocytes without Compound C pretreatment. Thus, CTRP3 increased the expression and secretion of adiponectin, leptin, visfatin, and apelin in 3T3-L1 adipocytes, while insulin resistance inhibited the effects. CTRP3 up-regulated the expression of adiponectin in 3T3-L1 adipocytes through AMPK signaling pathway.


Genetic contributions to disparities in preterm birth.
Ethnic disparity in preterm delivery between African Americans and European Americans has existed for decades, and is likely the consequence of multiple factors, including socioeconomic status, environment, and genetics. This review summarizes existing information on genetic variation and its association with preterm birth in African Americans. Candidate gene-based association studies, in which investigators have evaluated particular genes selected primarily because of their potential roles in the process of normal and pathologic parturition, provide evidence that genetic contributions from both mother and fetus account for some of the disparity in preterm births. To date, most attention has been focused on genetic variation in pro- and anti-inflammatory cytokine genes and their respective receptors. These genes, particularly the pro-inflammatory cytokine genes and their receptors, are linked to matrix metabolism because these cytokines increase expression of matrix degrading metalloproteinases. However, the role that genetic variants that are different between populations play in preterm birth (e.g. the SERPINH1 - G56 SNP) cannot yet be quantified. Future studies based on genome wide association or admixture mapping may reveal other genes that contribute to disparity in prematurity.


Pediatric neuroimaging findings and clinical presentations of COVID-19: A systematic review.
Symptoms from SARS-CoV-2 infection can involve multiple organ systems. Several reviews discussed the neurologic involvement and neuroimaging findings in adults but research on children is lacking. This study aimed to analyze the incidence of neurologic involvement in patients diagnosed with pediatric inflammatory multisystem syndrome temporally associated with COVID-19 (PIMS-TS) or multisystem inflammatory syndrome in children (MIS-C); and also to summarize current literature on possible neuroimaging findings in SARS-CoV-2 infected children. A literature search in six electronic databases was performed to retrieve case series, cohort studies, and cross-sectional studies on neurologic involvement in COVID-19 patients younger than 21 years of age published between December 2019 to September 2023, including COVID-19 patients. A total of 2224 patients with MIS-C from 10 cohorts and cross-sectional studies suggested that neurologic involvement in these subsets ranges from 8.5% to 32.1%. Symptoms included acute encephalitis, seizures, stroke, cranial nerve palsy, nausea/vomiting, and intracranial hypertension. Neuroradiology findings of 114 children from 50 case reports included splenial or acute disseminated encephalomyelitis (ADEM)-like lesions, cytotoxic brain edema, autoimmune demyelinating diseases, ischemic stroke and arteritis, venous thrombosis, intracranial hemorrhage, meningitis, posterior reversible encephalopathy syndrome, anti-N-methyl-D-aspartate receptor autoimmune encephalitis, acute hemorrhagic leukoencephalitis, hydrocephalus, olfactory bulb atrophy, cerebellitis, and acute necrotizing encephalitis. Radiologic findings of SARS-CoV-2 infection in the pediatric population are diverse. Neuroimaging studies should be considered in critically ill patients to rule out neurologic involvement and facilitate early interventions.


Some observations on protein metabolism in chromosomes of non-dividing cells.
1. The metabolism of chromosomal proteins has been studied in the pancreas, liver, and kidney of adult mice (a) by measuring the rates of glycine-N(15) incorporation into histones and residual chromosome fractions, and (b) by measuring the extent to which N(15), once incorporated into chromosomal proteins, is retained. 2. The uptake of isotopic nitrogen by these nuclear constituents was compared with that of protein fractions prepared from the cytoplasm by differential centrifugation in sucrose solutions. One such fraction, which comprises the bulk of the ribosenucleoprotein of the cell sediments as a pellet on high speed centrifugation. The supernatant remaining after this centrifugation is a fraction which, in the pancreas, is rich in the secretory enzymes synthesized by the cell. 3. A comparison of the rates of glycine-N(15) uptake shows that cytoplasmic ribonucleoprotein is the most active of the protein fractions analyzed. In the pancreas it meets the conditions required of a precursor for the secretory enzymes of the supernate. 4. In all tissues considered the rates of glycine-N(15) uptake into histone and residual chromosome fractions are lower, that for histone being the lowest of any of the protein components considered and that for residual protein approximating the over-all rate for cytoplasmic protein. 5. The effects of feeding and fasting upon glycine-N(15) incorporation have been studied. In the pancreas, feeding causes a sharp increase in N(15) uptake by the mixed tissue proteins and by the nucleoprotein and supernatant protein of the cytoplasm. There is a parallel increase in N(15) uptake by the chromosomal constituents-histone and residual protein. 6. A parallelism between N(15) uptake in cytoplasmic and chromosomal proteins is also observed in the liver and kidney when over-all protein metabolism is altered by feeding and fasting. 7. The responsiveness of the histones and residual proteins to changes in the environment has also been demonstrated in N(15) retention experiments. The loss of isotope once incorporated into chromosomal proteins is much more rapid in fed than in fasted animals.


DFI-seq identification of environment-specific gene expression in uropathogenic Escherichia coli.
During infection of the urinary tract, uropathogenic Escherichia coli (UPEC) are exposed to different environments, such as human urine and the intracellular environments of bladder epithelial cells. Each environment elicits a distinct bacterial environment-specific transcriptional response. We combined differential fluorescence induction (DFI) with next-generation sequencing, collectively termed DFI-seq, to identify differentially expressed genes in UPEC strain UTI89 during growth in human urine and bladder cells. DFI-seq eliminates the need for iterative cell sorting of the bacterial library and yields a genome-wide view of gene expression. By analysing the gene expression of UPEC in human urine we found that genes involved in amino acid biosynthesis were upregulated. Deletion mutants lacking genes involved in arginine biosynthesis were outcompeted by the wild type during growth in human urine and inhibited in their ability to invade or proliferate in the J82 bladder epithelial cell line. Furthermore, DFI-seq was used to identify genes involved in invasion of J82 bladder epithelial cells. 56 genes were identified to be differentially expressed of which almost 60% encoded hypothetical proteins. One such gene UTI89_C5139, displayed increased adhesion and invasion of J82 cells when deleted from UPEC strain UTI89. We demonstrate the usefulness of DFI-seq for identification of genes required for optimal growth of UPEC in human urine, as well as potential virulence genes upregulated during infection of bladder cell culture. DFI-seq holds potential for the study of bacterial gene expression in live-animal infection systems. By linking fitness genes, such as those genes involved in amino acid biosynthesis, to virulence, this study contributes to our understanding of UPEC pathophysiology.


Admissions of cats to animal welfare shelters in Melbourne, Australia.
Although the number of companion animal (pet) cats (Felis catus) in Australia is decreasing, there has not been a corresponding reduction in feline admissions to nonhuman animal welfare shelters. This study tracked 15,206 cat admissions to 1 large Melbourne shelter over a 12-month period. Data collected included factors believed indicative of the cats' source subpopulation, including body condition, injuries, and sociability. The majority (81.6%) of admissions were strays. Overall desexing levels were low (4%), even among caregiver (owner)-relinquished cats (12.8%). The high sociability of many stray cats and kittens suggests that many may be "semiowned" animals. Colony cats were typically thinner and in poorer health than other admissions. The pattern of kitten admissions suggests that many queens are producing 2 litters per season. The majority of cats admitted were euthanized, indicating that there is an oversupply of cats in Melbourne, Australia, and that strategies to reduce the euthanasia rate need to target the subpopulations of cats who contribute to the current oversupply.


Incidence and nature of dosing errors in paediatric medications: a systematic review.
In paediatric medicine, drug doses are usually calculated individually based on the patient's age, weight and clinical condition. Therefore, there are increased opportunities for, and a relatively high risk of, dosing errors in this setting. Consequently, a systematic literature review using several databases was conducted to investigate the incidence and nature of dosing errors in children; 16 studies were found to be relevant. Eleven of the 16 studies found that dosing errors are the most common type of medication error, three of the remaining studies found it to be the second most common type. This review of published research on medication errors therefore suggests that dosing errors are probably the most common type of error in the paediatric population. In addition, there was a great variation in the error rates reported; this is likely to be due to the differences in the medication error definitions and methodologies employed. For example, the dosing error rate determined using spontaneous reporting ranges from 0.03 per 100 admissions in the UK to 2 per 100 admissions in the US. Extrapolating this, if the under-reporting rate is about 1 in 100, then the true incidence would be around 50,000 paediatric dosing errors per year in England. The information available shows that dosing errors are not uncommon and that 10-fold overdoses caused by calculation errors have led to serious consequences. There is an urgent need to develop methods to reduce medication errors in children and dosing errors should be the first priority.


A curve of thresholds governs plague epizootics in Central Asia.
A core concept of infectious disease epidemiology is the abundance threshold, below which an infection is unable to invade or persist. There have been contrasting theoretical predictions regarding the nature of this threshold for vector-borne diseases, but for infections with an invertebrate vector, it is common to assume a threshold defined by the ratio of vector and host abundances. Here, we show in contrast, both from field data and model simulations, that for plague (Yersinia pestis) in Kazakhstan, the invasion threshold quantity is based on the product of its host (Rhombomys opimus) and vector (mainly Xenopsylla spp.) abundances, resulting in a combined threshold curve with hyperbolic shape. This shape implies compensation between host and vector abundances in permitting infection, which has important implications for disease control. Realistic joint thresholds, supported by data, should promote improved understanding, prediction and management of disease occurrence in this and other vector-borne disease systems.


Tube feed or not tube feed?
Tube feeding should always be considered relative to patient goals. Physicians should be prepared to discuss tube feeding as an option bearing in mind what evidence (or lack thereof) exists that tube feeding will help reach such goals.


Defining protective responses to pathogens: cytokine profiles in leprosy lesions.
The immunological mechanisms required to engender resistance have been defined in few infectious diseases of man, and the role of specific cytokines is unclear. Leprosy presents clinically as a spectrum in which resistance correlates with cell-mediated immunity to the pathogen. To assess in situ cytokine patterns, messenger RNA extracted from leprosy skin biopsy specimens was amplified by the polymerase chain reaction with 14 cytokine-specific primers. In lesions of the resistant form of the disease, messenger RNAs coding for interleukin-2 and interferon-gamma were most evident. In contrast, messenger RNAs for interleukin-4, interleukin-5, and interleukin-10 predominated in the multibacillary form. Thus, resistance and susceptibility were correlated with distinct patterns of cytokine production.


Change in health and self-perceptions of aging over 16 years: the role of psychological resources.
Self-perceptions of aging (SPA) are argued to be an indicator of the ability to adapt to heath decline in late life. Our objective was to examine the influence of psychological resources in maintaining positive self-perceptions of aging in the face of declining health in older adults. Time-varying change in health (medical conditions), physical functioning (ADLs), and psychological resources (expectancy of control and self-esteem) on change in SPA were examined over 16 years (5 waves) in a large representative sample (N = 1569) of older adults (65 + years at baseline) from the Australian Longitudinal Study of Aging. Multilevel structural equation models revealed mediating effects of psychological resources at the within-person level for the relationship between decline in ADLs and SPA. At the between-person level, the relationship between medical conditions and SPA was not mediated by psychological resources, whereas ADLs and SPA were shown to be indirectly associated through self-esteem and expectancy of control. Results demonstrate that maintaining self-esteem and an expectancy of personal control can buffer the effects of declining ADLs on perceptions of aging. Findings have clinical implications regarding psychological interventions aimed at improving resilience in older adults, which may ultimately increase health outcomes and quality of life.


Promoting prevention through the affordable care act: workplace wellness.
Public health in the United States can be improved by building workplace "cultures of health" that support healthy lifestyles. The Affordable Care Act (ACA), which includes the Prevention and Public Health Fund, will support a new focus on prevention and wellness, offering opportunities to strengthen the public's health through workplace wellness initiatives. This article describes the opportunity the ACA provides to improve worker wellness.


Patterns of health behavior in U.S. adults.
Associations between health-related behaviors are important for two reasons. First, disease prevention and health promotion depend on understanding both prevalence of health behaviors and associations among such behaviors. Second, behaviors may have synergistic effects on disease risk. We document patterns of adherence to recommendations concerning five behaviors (physical activity, tobacco use, alcohol consumption, fruit and vegetable consumption, and dietary fat intake) in U.S. adults (n = 15,425) using data from the Third National Health and Nutrition Examination Survey. Division of individuals into categories associated with adherence or nonadherence to lifestyle recommendations results in 32 patterns of adherence/nonadherence. Proportions of U.S. adults with 21 of 32 behavior patterns characterized here deviated from proportions expected if health behaviors are independent of each other. The two extreme patterns, all adherence (5.9%) and all nonadherence (4.9%), were found in about double the proportion expected. Age, gender, race/ethnicity, education, and income were associated with a number of patterns, including the two extremes. This analysis of behavior patterns highlights population subgroups of public health importance, provides a benchmark for studies of multivariate associations between health behaviors, and supports a multidimensional model of health behavior.


Heterogeneity of the glutathione transferase genes encoding enzymes responsible for insecticide degradation in the housefly.
One of the four glutathione-S-transferases (GST) that is overproduced in the insecticide-resistant Cornell-R strain of the housefly (Musca domestica) produces an activity that degrades the insecticide dimethyl parathion and conjugates glutathione to lindane. In earlier work, it was shown that the resistant Cornell-R carries an amplification, probably a duplication, of one or more of its GST loci and that this amplification is directly related to resistance. Using polymerase chain reaction (PCR) amplification with genomic DNA, multiple copies of the gene encoding the parathion-degrading activity (called MdGst-3) were subcloned from both the ancestral, insecticide-susceptible strain BPM and from the insecticide-resistant Cornell-R. In BPM, three different MdGst-3 genes were identified while in Cornell-R, 12 different MdGst-3 sequences were found that, though closely related to ancestral genes, had diverged by a few nucleotides. This diversity in MdGst-3 genomic sequences in Cornell-R is reflected in the expressed sequences, as sampled through a cDNA bank. Population heterozygosity cannot account for these multiple GST genes. We suggest that selection for resistance to insecticides has resulted in not only amplification of the MdGst-3 genes but also in the divergence of sequence between the amplified copies.


The prevalence of pleural effusions in pre-eclampsia: an ultrasound study.
A prospective ultrasound study was undertaken to investigate the prevalence of pleural effusion in patients with moderate or severe pre-eclampsia. The costophrenic angles of 34 consecutive patients were scanned postpartum with a real-time sector scanner. Six patients had pleural effusions. These patients did not have a greater degree of hypertension or proteinuria than the group without pleural effusion but had early severe disease requiring early delivery. The prematurity of these infants resulted in tenfold increase in perinatal death.


Cognitive-linguistic profiles of Chinese typical-functioning adolescent dyslexics and high-functioning dyslexics.
Dyslexia is a developmental disability affecting the acquisition of reading and writing skills, and its developmental nature makes longitudinal research of great importance. This study therefore investigated the cognitive-linguistic profiles of the typical-functioning dyslexics and high-functioning dyslexics with longitudinal cohorts of Chinese-speaking adolescents diagnosed with childhood dyslexia. These two dyslexic groups of fifty students (with 25 typical-functioning dyslexics) were assessed in Grade 2 (Time 1) and in Grade 8 (Time 2), whereas 25 typically developing controls were assessed at Time 2. Students were administered measures of phonological awareness, morphological skills, visual-orthographic knowledge, rapid naming, verbal working memory, and literacy skills. Results showed that, at Time 2, both dyslexic groups performed less well than the control group on most of the measures. Deficits in rapid naming were particularly salient in both dyslexic groups. Comparing the two dyslexic groups, the typical-functioning dyslexics had more multiple deficits than the high-functioning dyslexics. Findings highlight the importance of rapid naming deficits as potential universal causes of dyslexia and the utility of targeting visual-orthographic knowledge and morphological skills in supporting the development of dyslexic adolescents.


Néel Spin-Orbit Torque Driven Antiferromagnetic Resonance in Mn_{2}Au Probed by Time-Domain THz Spectroscopy.
We observe the excitation of collective modes in the terahertz (THz) range driven by the recently discovered Néel spin-orbit torques (NSOTs) in the metallic antiferromagnet Mn_{2}Au. Temperature-dependent THz spectroscopy reveals a strong absorption mode centered near 1 THz, which upon heating from 4 to 450 K softens and loses intensity. A comparison with the estimated eigenmode frequencies implies that the observed mode is an in-plane antiferromagnetic resonance (AFMR). The AFMR absorption strength exceeds those found in antiferromagnetic insulators, driven by the magnetic field of the THz radiation, by 3 orders of magnitude. Based on this and the agreement with our theory modeling, we infer that the driving mechanism for the observed mode is the current-induced NSOT. Here the electric field component of the THz pulse drives an ac current in the metal, which subsequently drives the AFMR. This electric manipulation of the Néel order parameter at high frequencies makes Mn_{2}Au a prime candidate for antiferromagnetic ultrafast memory applications.


Risk factors for intraoperative portal vein thrombosis in pediatric living donor liver transplantation.
Pathologic changes of the recipient native portal venous system may cause thrombosis of the portal vein, especially in pediatric living donor liver transplantation (LDLT). This study assessed the utility of Doppler ultrasound (US) for the detection of intraoperative portal vein occlusion and identification of predisposing risk factors in the recipients. Seventy-three pediatric recipients who underwent LDLT at Chang Gung Memorial Hospital, Taiwan, from 1994 to 2002 were included. Preoperative and intraoperative Doppler US evaluation of the portal vein was performed. Age, body weight, native liver disease, type of graft, graft recipient weight ratio (GRWR), type of portal anastomosis, portal velocity, portal venous size and presence of portosystemic shunt were analyzed for statistical significance of predisposing risk factors. Eight episodes of intraoperative portal vein thrombosis, with typical findings of absent Doppler flow in portal vein and prominent hepatic artery with a resistant index lower than 0.5 (p < 0.001), were detected during transplantation, which was then corrected by thrombectomy and re-anastomosis. Children age < or =1 yr (p = 0.025), weight < or =10 kg (p = 0.024), low portal flow < or =7 cm/s (p = 0.021), portal venous size < or =4 mm (p = 0.001), and GRWR >3 (p < 0.017) were all risk factors for intraoperative portal vein thrombosis. Doppler US is essential in the preoperative evaluation, early detection and monitoring of outcome of the portal vein in liver transplant.


Immunological anomalies and thrombocytopenia in 117 dogs and cats diagnosed with chronic fatigue syndrome (CFS).
Retrospective analysis of immune dysfunctions found in 55 dogs and 62 cats diagnosed with Chronic Fatigue Syndrome (CFS), revealed leukopenia in 11% of dogs (n = 6) and 22.5% of cats (n = 14), lymphopenia in 14.5% of dogs (n = 8) and 10% of cats (n = 6), hypogammaglobulinaemia in 9% of dogs (n = 5) and 13% of cats (n = 8) and thrombocytopenia in 20% of dogs (n = 11) and 68% of cats (n = 42). All patients had creatine kinase enzyme levels above the normal range (CK = 5-100 IU/L) and carried micrococcus-like organisms on erythrocytes. Blood cultures proved positive for Staphylococcus spp. in 16 cases. After low-dosage arsenic-based therapy (thiacetarsamide sodium) all animals experienced complete clinical remission. Subsequent controls demonstrated immune restoration in 4 representative FIV-FeLV negative cats, previously diagnosed with CFS associated with leukopenia, lymphopenia, hypogammaglobulinaemia and thrombocytopenia. The main conclusion is that a CFS-like disease in dogs and cats, characterised by the common hallmarks of high CK levels, absence of known causes of chronic fatigue in animals and presence of micrococcus-like organisms in the blood, can be associated with humoral and/or cellular immune deficiencies in 9-22.5% of cases and with thrombocytopenia in 20-68% of cases. Considerations are made on the possible role of micrococci in the aetiology of the condition and on the similarities with CFS in humans.