The biogeochemical controls of N2O production and emission in landfill cover soils: the role of methanotrophs in the nitrogen cycle.
Emissions of N2O from cover soils of both abandoned (> 30 years) and active landfills greatly exceed the maximum fluxes previously reported for tropical soils, suggesting high microbial activities for N2O production. Low soil matrix potentials (<-0.7 MPa) indicate that nitrification was the most likely mechanism of N2O formation during most of the time of sampling. Soil moisture had a strong influence on N2O emissions. The production of N2O was stimulated by as much as 20 times during laboratory incubations, when moisture was increased from -2.0 MPa to -0.6 MPa. Additional evidence from incubation experiments and delta13C analyses of fatty acids (18:1) diagnostic of methanotrophs suggests that N2O is formed in these soils by nitrification via methanotrophic bacteria. In a NH3(g)-amended landfill soil, the rate of N2O production was significantly increased when incubated with 100 ppmv methane compared with 1.8 ppmv (atmospheric) methane. Preincubation of a landfill soil with 1% CH4 for 2 weeks resulted in higher rates of N2O production when subsequently amended with NH3(g) relative to a control soil preincubated without CH4. At one location, at the soil depth (9-16 cm) of maximum methane consumption and N2O production, we observe elevated concentrations of organic carbon and nitrogen and distinct minima in delta15N (+1.0%) and delta13C (-33.8%) values for organic nitrogen and organic carbon respectively. A delta13C value of -39.3% was measured for 18:1 carbon fatty acids in this soil, diagnostic of type II methanotrophs. The low delta15N value for organic nitrogen is consistent with N2 fixation by type II methanotrophs. These observations all point to a methanotrophic origin for the organic matter at this depth. The results of this study corroborate previous reports of methanotrophic nitrification and N2O formation in aqueous and soil environments and suggest a predominance of type II rather than type I or type X methanotrophs in this landfill soil.


Reward and Cognition: Integrating Reinforcement Sensitivity Theory and Social Cognitive Theory to Predict Drinking Behavior.
Both Reinforcement Sensitivity Theory and Social Cognitive Theory have been applied to understanding drinking behavior. We propose that theoretical relationships between these models support an integrated approach to understanding alcohol use and misuse. We aimed to test an integrated model in which the relationships between reward sensitivity and drinking behavior (alcohol consumption, alcohol-related problems, and symptoms of dependence) were mediated by alcohol expectancies and drinking refusal self-efficacy. Online questionnaires assessing the constructs of interest were completed by 443 Australian adults (M age = 26.40, sd = 1.83) in 2013 and 2014. Path analysis revealed both direct and indirect effects and implicated two pathways to drinking behavior with differential outcomes. Drinking refusal self-efficacy both in social situations and for emotional relief was related to alcohol consumption. Sensitivity to reward was associated with alcohol-related problems, but operated through expectations of increased confidence and personal belief in the ability to limit drinking in social situations. Conversely, sensitivity to punishment operated through negative expectancies and drinking refusal self-efficacy for emotional relief to predict symptoms of dependence. Two pathways relating reward sensitivity, alcohol expectancies, and drinking refusal self-efficacy may underlie social and dependent drinking, which has implications for development of intervention to limit harmful drinking.


[A case of Poncet's disease (tuberculous rheumatism) in a patient with chronic renal failure undergoing hemodialysis therapy].
A 78-year-old man who was undergoing hemodialysis therapy was admitted to our hospital because of sore throat, remittent cervical lymphadenopathy, and polyarthritis over the preceding 4 weeks. On admission, he had bilateral cervical lymphadenopathy. He complained of arthralgia associated with tenderness, warmth and swelling of both elbows, left side wrist and left shoulder joint. The C-reactive protein level on admission was 15.3 mg/dl. Rheumatoid factor, antinuclear antibodies, tuberculin skin test and blood culture were negative. Joint fluid was not aspirated. Radiographs of the joints did not reveal any abnormalities. Acid-fast bacilli were demonstrated in the smear of the cervical lymph node with a fluorochrome rhodamine-auramine stain. Mycobacterium tuberculosis DNA was identified by polymerase chain reaction. We found the presence of caseating granuloma on the biopsy specimens and M.tuberculosis was detected from culture. At that point, we diagnosed this patient as having tuberculous lymphadenitis. His general symptoms resolved rapidly after starting with a three-drug regimen consisting of isoniazid, rifampin and pyrazinamide. His polyarthritis also improved dramatically. Finally we considered that his polyarthritis was tuberculous rheumatism, also called Poncet's disease. Poncet's disease is characterized by sterile polyarthritis during active tuberculosis infection. It is considered a reactive arthritis, which is a different entity from tuberculous arthritis. Although this is a rare disease, we should be aware of it in hemodialysis patient clinics, because the incidence of tuberculosis infection has been reported to be increasing in patients with end-stage renal failure.


Functional consequences of bidirectional promoters.
Several studies have shown that promoters of protein-coding genes are origins of pervasive non-coding RNA transcription and can initiate transcription in both directions. However, only recently have researchers begun to elucidate the functional implications of this bidirectionality and non-coding RNA production. Increasing evidence indicates that non-coding transcription at promoters influences the expression of protein-coding genes, revealing a new layer of transcriptional regulation. This regulation acts at multiple levels, from modifying local chromatin to enabling regional signal spreading and more distal regulation. Moreover, the bidirectional activity of a promoter is regulated at multiple points during transcription, giving rise to diverse types of transcripts.


Wavelength locking of CW and Q-switched Er(3+) microchip lasers to acetylene absorption lines using pump-power modulation.
We show that modulating the diode-pump power of a microchip solid-state laser enables to lock its wavelength to a reference molecular line. The method is applied to two different types of Er,Yb:glass monolithic microchip lasers operating at 1.53 microm. First, wavelength locking of a continuous-wave dual-polarization microchip laser to acetylene absorption lines is demonstrated, without using any additional modulator, internal or external. We then show that, remarkably, this simple method is also suitable for stabilizing a passively Q-switched microchip laser. A pulsed wavelength stability of 10(-8) over 1 hour is readily observed. Applications to lidars and to microwave photonics are discussed.


Population prevalence rates of birth defects: a data management and epidemiological perspective.
The Victorian Birth Defects Register (VBDR) is a population-based surveillance system with a primary function of monitoring trends in birth defects. This paper outlines the processes undertaken in Victoria, Australia, to obtain population prevalence rates of birth defects and investigates the effect on the prevalence rates of variations in collection and processing tasks. It includes all birth defects that were notified to the VBDR by 31 December 2004. The overall prevalence rate of birth defects in Victoria for 2003 was 4.0%, with an overall accuracy rate of 88%. However, this proportion varied according to what birth defects were included, the age by which birth defects were diagnosed, changes to sources of ascertainment, inclusion of terminations of pregnancy, or reporting by cases rate (infants affected) or birth defect rate (individual birth defects). Taking all of these factors into consideration, we are confident that 4.0% is an accurate population prevalence rate of birth defects in Victoria for 2003.


Controversial evidence regarding the functional importance of presynaptic alpha receptors.
alpha-Adrenergic agonists have been reported to decrease the release of neuronal norepinephrine (NE) via presynaptic alpha 2 receptors when studied under in vitro conditions. Within the last several years studies have been performed in the intact animal to determine whether this presynaptic mechanism is a pharmacological artifact or whether it plays a functional role in cardiovascular physiology. In the intact renal vascular bed clonidine, oxymetazoline, and NE did not decrease stimulation-induced vasoconstrictor responses relative to constrictor responses produced by exogenous NE. Similarly, the alpha-receptor antagonists yohimbine and phentolamine did not potentiate constrictor responses induced by renal nerve stimulation. Studies involving the heart produce contradictory results. Clonidine and NE have been reported to decrease or have no effect on chronotropic responses to cardiac nerve stimulation. Phenoxybenzamine and desipramine have been reported to increase the overflow of NE in coronary sinus blood during cardiac nerve stimulation but not to potentiate chronotropic responses. Thus, this brief review points out that the functional importance of a presynaptic mechanism to modulate the release of NE still remains to be determined.


Bone-marrow-derived cells for enhancing collateral development: mechanisms, animal data, and initial clinical experiences.
Initial animal studies of single angiogenic agents, such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), generated enthusiasm for the concept that these agents might enhance collateral development and thereby provide alternative therapies for patients with vascular disease not amenable to traditional revascularization. The enthusiasm, apparently justified by the subsequent results of small nonrandomized phase-I clinical trials, was then tempered by the subsequent disappointing results of randomized clinical trials. In light of these disappointing results, investigators have pursued alternative strategies in an attempt to improve tissue perfusion. One such strategy is the utilization of bone marrow-derived cell therapy. This review discusses mechanistic pathways mediating the effects of such cell therapy, summarizes the animal and early clinical experience, and speculates on the potential of genetic manipulation of bone marrow-derived cells in an attempt to further enhance their potency.


Binding and internalization of heparin by vascular smooth muscle cells.
Previous work from our laboratory has demonstrated that heparin specifically inhibits the proliferation of vascular smooth muscle cells in vivo and in vitro. In this paper, we examine the binding and mode of internalization of heparin by smooth muscle cells. For these studies, radiolabeled and fluoresceinated (FITC) heparin probes were synthesized that retained their antiproliferative capacity. Binding of 3H-heparin to these cells occurs via specific, high-affinity binding sites (Kd = 10(-9) M, 100,000 binding sites per cell). Approximately 80% of the heparin bound to the cell surface was shed into the culture medium within 2 hr. The heparin that was left on the cell surface was internalized with biphasic kinetics. Approximately 50% of the bound material was internalized within 2 hr. After this initial rapid uptake, the rate slowed substantially, with the remaining heparin requiring 1-2 days to be internalized. Binding and uptake of FITC heparin was monitored using video image intensification fluorescence microscopy. When smooth muscle cells were exposed to FITC heparin at 4 degrees C, a diffuse surface staining pattern was observed. After warming the cells to 37 degrees C, intensely fluorescent vesicles were seen superimposed over the diffuse surface staining within 2 min. After 15 min at 37 degrees C, numerous large punctate vesicles were seen inside the cell. After 2 hr these vesicles had concentrated in the perinuclear region. This pattern of uptake, when considered along with the presence of specific, high-affinity binding sites and the initial rapid uptake of 3H-heparin, suggests that heparin enters smooth muscle cells by both receptor-mediated and other endocytic pathways.


Reducing the Burden of Disease Associated With Periprosthetic Fractures: Prevention and the Need for Improved Perioperative Care.
The management of periprosthetic fractures remains challenging and controversial. There continues to be a significant burden of disease and substantial resource implications associated with fractures following total joint arthroplasty. Achieving consensus opinions regarding the prevention and treatment of this problem has important implications given the profound effect on patient outcomes. Multidisciplinary care in the preoperative and postoperative settings is critical, with a specific focus on bone health.


Seeding the meiotic DNA break machinery and initiating recombination on chromosome axes.
Programmed DNA double-strand break (DSB) formation is a unique meiotic feature that initiates recombination-mediated linking of homologous chromosomes, thereby enabling chromosome number halving in meiosis. DSBs are generated on chromosome axes by heterooligomeric focal clusters of DSB-factors. Whereas DNA-driven protein condensation is thought to assemble the DSB-machinery, its targeting to chromosome axes is poorly understood. We discovered in mice that efficient biogenesis of DSB-machinery clusters requires seeding by axial IHO1 platforms, which are based on a DBF4-dependent kinase (DDK)-modulated interaction between IHO1 and the chromosomal axis component HORMAD1. IHO1-HORMAD1-mediated seeding of the DSB-machinery on axes ensures sufficiency of DSBs for efficient pairing of homologous chromosomes. Without IHO1-HORMAD1 interaction, residual DSBs depend on ANKRD31, which enhances both the seeding and the growth of DSB-machinery clusters. Thus, recombination initiation is ensured by complementary pathways that differentially support seeding and growth of DSB-machinery clusters, thereby synergistically enabling DSB-machinery condensation on chromosomal axes.


Global networks and global change-induced tipping points.
The existence of "tipping points" in human-environmental systems at multiple scales-such as abrupt negative changes in coral reef ecosystems, "runaway" climate change, and interacting nonlinear "planetary boundaries"-is often viewed as a substantial challenge for governance due to their inherent uncertainty, potential for rapid and large system change, and possible cascading effects on human well-being. Despite an increased scholarly and policy interest in the dynamics of these perceived "tipping points," institutional and governance scholars have yet to make progress on how to analyze in which ways state and non-state actors attempt to anticipate, respond, and prevent the transgression of "tipping points" at large scales. In this article, we use three cases of global network responses to what we denote as global change-induced "tipping points"-ocean acidification, fisheries collapse, and infectious disease outbreaks. Based on the commonalities in several research streams, we develop four working propositions: information processing and early warning, multilevel and multinetwork responses, diversity in response capacity, and the balance between efficiency and legitimacy. We conclude by proposing a simple framework for the analysis of the interplay between perceived global change-induced "tipping points," global networks, and international institutions.


[The development of lipid and anthropometric parameters in the treatment of pre-pubertal obese patients].
Relationships have been found between obesity and changes in serum lipid levels which may lead to antherogenic lipid profiles. There are few studies treating obesity and showing the possibility of improving lipid abnormalities in prepubertal obese patients. One hundred and three obese patients ranging from 5.3 to 9.9 years old have been studied. Anthropometric (height, weight, body mass index-BMI-, and subscapular and triceps skinfolds) and lipid (total and lipoprotein cholesterol, triglycerides, apoprotein A1 and B) parameters were measured both at the beginning of the study and after six months of diet treatment. Patients were included in three groups according to their response to treatment: good response (GR), no response (NR) and bad response (BR), if the difference in BMI was less than 1 point (< 1), between -1 and +1 and more than 1 point (> 1), respectively. Forty-one patients (39.8%) were noncompliant. Of the remaining sixty-two, 41 (66%) had a GR, 16 (25.8% NR and 5 (8%) BR. The obese patients showed a significantly lower HDL-C (38.8 +/- 15.6 vs 48.3 +/- 10.2 mg/dl, p < 0.01) in comparison to the control group. GR patients showed a statistically significant increase in HDL-C (48.2 +/- 9.1 vs 54.9 +/- 12.0 mg/dl, p < 0.01) and apoprotein A1 (126.7 +/- 17.3 vs 136.0 +/- 17.4 mg/dl, p < 0.05) levels at the end of the study. There was no statistically significant difference in serum lipid levels in the other two groups. There was no statistically significant correlation between serum lipid levels and anthropometric parameters. The difference between final minus initial value in both lipid and anthropometric parameters were not correlated. Sixteen patients (17.7%) had pathological serum lipid levels, 15 of them showing hypertriglyceridemia, that disappeared in GR patients. Prepubertal obese patients show alterations in lipid profiles and this is not correlated with anthropometric parameters. The improvement in these anthropometric parameters improve the lipid profile. Initial pathologic serum lipid levels in GR patients become normalized.


Modular stems in DDH.
The Modulus (Lima-Lto) system has been created on the association of a conical stem and a modular neck in order to address the so called "difficult hip". Modularity can maximize the options for a correct reconstruction in a total hip replacement of the coxofemoral anatomy as well as biomechanics. Modulus should be used in CDH, primary hip arthritis, the sequelae of osteotomies and in each case in which we face a congenital or acquired hip deformity. The Modulus stem has been commonly utilised in association with the Delta cup (Lima-Lto) with the chance to use big diameter heads (32-36 mm) and ceramic on ceramic coupling. Modulus has been used in association with Delta cup since November 2002. 51 patients affected by CDH have been treated. Clinical and radiographic results can be considered very good. The average evaluation based on Merle D'Aubigné schedule is equal to 17.5 with a significant increase in the results with respect to the preoperatory score (with an average score equal to 10). In the light of the above, Modulus should be considered a valuable system to optimize the results of total hip replacement also in those more complex situations with a modified femoral morphology, allowing the restoration of a normal biomechanics in terms of off-set and anteversion with benefit in terms of stability and length of the implant as well as in terms of satisfaction of the patient as far as limb length and ROM are concerned. The association of Modulus with big diameter heads gives a higher guarantee in terms of duration of the implant and restoration of the functionality in young patients with a serious deformity and increased functional demands.


Posttraumatic stress symptomatology and cancer.
The extant nosological formulations of the American Psychiatric Association denotes that Posttraumatic Stress Disorder (PTSD) maybe predicated upon some life threatening experience. Historically, combat, robbery, rape, and serious accidents have been included as traumatogenetic stressors. Only recently has life-threatening illness been considered as a traumatogenetic stressor. This paper reviews the relativity between cancer and posttraumatic stress.


Veterinary drug therapies used for undesirable behaviours in UK dogs under primary veterinary care.
Undesirable behaviours (UBs) in dogs are common and important issues with serious potential welfare consequences for both the dogs and their owners. This study aimed to investigate the usage of drug therapy for UBs in dogs and assess demographic risk factors for drug-prescribed UBs within the dog population under primary-care veterinary care in the UK in 2013. Dogs receiving drug therapy for UB were identified through the retrospective analysis of anonymised electronic patient records in VetCompass™. Risk factor analysis used multivariable logistic regression modelling. The study population comprised 103,597 dogs under veterinary care in the UK during 2013. There were 413 drug-prescribed UBs recorded among 404 dogs. The prevalence of dogs with at least one UB event treated with a drug in 2013 was 0.4%. Multivariable modelling identified 3 breeds with increased odds of drug-prescribed UB compared with crossbred dogs: Toy Poodle (OR 2.75), Tibetan Terrier (OR 2.68) and Shih-tzu (OR 1.95). Increasing age was associated with increased odds of drug-prescribed UB, with dogs ≥ 12 years showing 3.1 times the odds compared with dogs < 3 years. Neutered males (OR 1.82) and entire males (OR 1.50) had increased odds compared with entire females. The relatively low prevalence of dogs with at least one UB event that was treated with a drug in 2013 could suggest that opportunities for useful psychopharmaceutical intervention in UBs may be being missed in first opinion veterinary practice. While bodyweight was not a significant factor, the 3 individual breeds at higher odds of an UB treated with a behaviour modifying drug all have a relatively low average bodyweight. The current results also support previous research of a male predisposition to UBs and it is possible that this higher risk resulted in the increased likelihood of being prescribed a behaviour modifying drug, regardless of neuter status.


[The method of reoperation on the nasal septum for its deformity].
The author emphasizes the necessity of reoperation on the nasal septum if the previous surgery failed to correct it adequately and a positive functional result was not achieved. A technique of reoperation in different modifications is proposed with a differential approach depending on the deformity type, scope of surgical intervention on its osteocartilaginous base, presence of complications (synechia, perforation). Data on the reoperation on the nasal septum made within 14 years are presented for 196 patients.


Associations between Blood Zinc Concentrations and Sleep Quality in Childhood: A Cohort Study.
Little evidence is available regarding the relationship between zinc and sleep in school children. The present study aimed to examine the cross-sectional and longitudinal associations between blood zinc concentrations and sleep quality throughout childhood. A total of 1295 children from the Jintan Child Cohort in China were included in this study. Venous blood sample of zinc and subjective sleep data were collected when the children were at preschool age (3-5 years old) and early adolescence (11-15 years old). Odds ratios (ORs) reflect the odds of the sleep quality/subdomain being at a greater impairment level associated with 1 unit increase in log zinc concentration. Cross-sectional analyses showed negative correlation of blood zinc concentrations with insufficient sleep duration (OR = 0.432, p = 0.002), sleep disturbances (OR = 0.454, p = 0.009) and poor sleep quality (OR = 0.559, p = 0.049) in adolescence, but no association at preschool age (p > 0.05). Longitudinal analyses indicated that blood zinc concentrations at preschool age predict poor sleep efficiency (OR = 0.186, p = 0.000) and poor sleep quality (OR = 0.358, p = 0.020) in adolescence. Our findings suggest that sufficient zinc concentration is associated with good sleep quality, dependent on the developmental stage in childhood. Future interventional research is warranted to examine the short and long-term effect of zinc status on sleep heath.


Combined Treatment of Progressive Encephalitis in an X-linked Agammaglobulinemia Patient.
Most patients with X-linked agammaglobulinemia are susceptible to infections, while some cases also suffer from inflammatory or autoimmune complications. We describe a patient with progressive encephalitis who improved after the use of immunomodulatory treatment with corticosteroids, fluoxetine, and nitazoxanide. In most of the cases the evolution of the progressive encephalitis is complicated and catastrophic. Based on our experience and the review of the literature, we propose the use of this combined treatment to control this devastating complication.


The methylenetetrahydrofolate reductase (MTHFR) 677C-->T mutation and cardiovascular risk--A case of ischemic stroke and acute myocardial infarction.
The authors report the case of a 39-year-old male patient who had an ischemic stroke (complete infarction of right anterior cerebral circulation) and an acute myocardial infarction during the same year. Molecular study revealed he was homozygous for the 677C-->T mutation in the gene coding for methylenetetrahydrofolate reductase, a key enzyme of folate metabolism; deficiency of this enzyme is associated with increased cardiovascular risk and neurological lesions. Some considerations are put forward about hyperhomocysteinemia and the MTHFR 677C-->T mutation as cardiovascular risk factors.


Temporal regulation of morphogenetic events in Saccharomyces cerevisiae.
Tip growth in fungi involves highly polarized secretion and modification of the cell wall at the growing tip. The genetic requirements for initiating polarized growth are perhaps best understood for the model budding yeast Saccharomyces cerevisiae. Once the cell is committed to enter the cell cycle by activation of G1 cyclin/cyclin-dependent kinase (CDK) complexes, the polarity regulator Cdc42 becomes concentrated at the presumptive bud site, actin cables are oriented toward that site, and septin filaments assemble into a ring around the polarity site. Several minutes later, the bud emerges. Here, we investigated the mechanisms that regulate the timing of these events at the single-cell level. Septin recruitment was delayed relative to polarity establishment, and our findings suggest that a CDK-dependent septin "priming" facilitates septin recruitment by Cdc42. Bud emergence was delayed relative to the initiation of polarized secretion, and our findings suggest that the delay reflects the time needed to weaken the cell wall sufficiently for the cell to bud. Rho1 activation by Rom2 occurred at around the time of bud emergence, perhaps in response to local cell-wall weakening. This report reveals regulatory mechanisms underlying the morphogenetic events in the budding yeast.


Targeting opioid receptor heterodimers: strategies for screening and drug development.
G-protein-coupled receptors are a major target for the development of new marketable drugs. A growing number of studies have shown that these receptors could bind to their ligands, signal, and be internalized as dimers. Most of the evidence comes from in vitro studies, but recent studies using animal models support an important role for dimerization in vivo and in human pathologies. It is therefore becoming highly relevant to include dimerization in screening campaigns: the increased complexity reached by the ability to target 2 receptors should lead to the identification of more specific hits that could be developed into drugs with fewer side effects. In this review, we have summarized results from a series of studies characterizing the properties of G-protein-coupled receptor dimers using both in vitro and in vivo systems. Since opioid receptors exist as dimers and heterodimerization modulates their pharmacology, we have used them as a model system to develop strategies for the identification of compounds that will specifically bind and activate opioid receptor heterodimers: such compounds could represent the next generation of pain relievers with decreased side effects, including reduced drug abuse liability.


Analysis of microbial community structure and diversity in the thermophilic anaerobic digestion of waste activated sludge.
The microbial community structures in the thermophilic anaerobic digestion (TAD) of waste activated sludge (WAS) and WAS were analyzed with molecular biological techniques including real-time polymerase chain reaction (PCR) and cloning. The microbial community of TAD had less diversity than that of WAS, and the sequences obtained in WAS were not present in TAD by the cloning analysis. In the TAD bacterial clone library, 97.5% of total clones were affiliated with the phylum Firmicutes and 73.1% with the genus Coprothermobacter. Real-time PCR and cloning analysis revealed that the number of Methanosarcina thermophila, which is an acetoclastic methanogen, is larger than that of Methanoculleus thermophilus, which is a hydrogenotrophic methanogen, in terms of the numbers of copies of 16S ribosomal DNA (rDNA).


A general intermolecular force field based on tight-binding quantum chemical calculations.
A black-box type procedure is presented for the generation of a molecule-specific, intermolecular potential energy function. The method uses quantum chemical (QC) information from our recently published extended tight-binding semi-empirical scheme (GFN-xTB) and can treat non-covalently bound complexes and aggregates with almost arbitrary chemical structure. The necessary QC information consists of the equilibrium structure, Mulliken atomic charges, charge centers of localized molecular orbitals, and also of frontier orbitals and orbital energies. The molecular pair potential includes model density dependent Pauli repulsion, penetration, as well as point charge electrostatics, the newly developed D4 dispersion energy model, Drude oscillators for polarization, and a charge-transfer term. Only one element-specific and about 20 global empirical parameters are needed to cover systems with nuclear charges up to radon (Z = 86). The method is tested for standard small molecule interaction energy benchmark sets where it provides accurate intermolecular energies and equilibrium distances. Examples for structures with a few hundred atoms including charged systems demonstrate the versatility of the approach. The method is implemented in a stand-alone computer code which enables rigid-body, global minimum energy searches for molecular aggregation or alignment.


New insights and challenges in mismatch repair: getting over the chromatin hurdle.
DNA mismatch repair (MMR) maintains genome stability primarily by repairing DNA replication-associated mispairs. Because loss of MMR function increases the mutation frequency genome-wide, defects in this pathway predispose affected individuals to cancer. The genes encoding essential eukaryotic MMR activities have been identified, as the recombinant proteins repair 'naked' heteroduplex DNA in vitro. However, the reconstituted system is inactive on nucleosome-containing heteroduplex DNA, and it is not understood how MMR occurs in vivo. Recent studies suggest that chromatin organization, nucleosome assembly/disassembly factors and histone modifications regulate MMR in eukaryotic cells, but the complexity and importance of the interaction between MMR and chromatin remodeling has only recently begun to be appreciated. This article reviews recent progress in understanding the mechanism of eukaryotic MMR in the context of chromatin structure and dynamics, considers the implications of these recent findings and discusses unresolved questions and challenges in understanding eukaryotic MMR.


Clopidogrel, aspirin and proton pump inhibition after percutaneous valve implants: an update.
This paper reviews literary evidence on antithrombotic therapies currently employed in TAVR to assess validity and efficacy; duration and modality are also considered. In the absence of firm guidelines and reliable trial results, we analyze current knowledge of interaction between PPI and antithrombotic drugs. TAVR has been associated with Double Antiplatelet Therapy since 2002. This was an empirical approach for a new stentmounted tissue valve to prevent early and late MACCE that affect survival and quality of life. Systematic searches of major bibliographic databases, contact with experts in the field, and review of primary articles, review papers, and guidelines has been performed. We analyze TAVR features and pitfalls in existing trials to understand which therapy would fit patients better and we confront these with established clinical practice guidelines of the population treated for cardiovascular disease. TAVR is a new technology that compresses a tissue valve onto an expandable stent. Technical and procedural issues have been solved, but strokes and major bleeding still affect patients' life despite double antiplatelet therapy given to reduce MACCE. To balance pros and cons, antithrombotic therapy with Warfarin or new anticoagulants can be used in patients with previous AF or NOAF to prevent stroke; while single antiplatelet with PPI is a better alternative in patients with liver disease, gastric ulcer or drug abuse to avoid bleeding events. While waiting for randomized trials, a tailored therapy based upon physician's experience and close patient follow-up is the safest, most effective treatment.


Parasites of firebugs in Austria with focus on the "micro"-diversity of the cosmopolitan trypanosomatid Leptomonas pyrrhocoris.
In this work, we investigated parasites of the firebug Pyrrhocoris apterus in Austria and demonstrated that in addition to the extensively studied Leptomonas pyrrhocoris, it can also be infected by Blastocrithidia sp. and by a mermithid, which for the first time has been characterized using molecular methods. This diversity can be explained by the gregarious lifestyle, as well as the coprophagous and cannibalistic behavior of the insect hosts that makes them susceptible to various parasites. In addition, we showed no tight association of the L. pyrrhocoris haplotypes and geographical locations (at least, considering the relatively small scale of locations in Austria) implying that the natural populations of L. pyrrhocoris are mixed due to the mobility of their firebug hosts.


American Society of Clinical Oncology policy statement update: genetic testing for cancer susceptibility.
As the leading organization representing cancer specialists involved in patient care and clinical research, the American Society of Clinical Oncology (ASCO) reaffirms its commitment to integrating cancer risk assessment and management, including molecular analysis of cancer predisposition genes, into the practice of oncology and preventive medicine. The primary goal of this effort is to foster expanded access to, and continued advances in, medical care provided to patients and families affected by hereditary cancer syndromes. The 1996 ASCO Statement on Genetic Testing for Cancer Susceptibility set forth specific recommendations relating to clinical practice, research needs, educational opportunities, requirement for informed consent, indications for genetic testing, regulation of laboratories, and protection from discrimination, as well as access to and reimbursement for cancer genetics services. In updating this Statement, ASCO endorses the following principles: Indications for Genetic Testing: ASCO recommends that genetic testing be offered when 1) the individual has personal or family history features suggestive of a genetic cancer susceptibility condition, 2) the test can be adequately interpreted, and 3) the results will aid in diagnosis or influence the medical or surgical management of the patient or family members at hereditary risk of cancer. ASCO recommends that genetic testing only be done in the setting of pre- and post-test counseling, which should include discussion of possible risks and benefits of cancer early detection and prevention modalities. Special Issues in Testing Children for Cancer Susceptibility: ASCO recommends that the decision to offer testing to potentially affected children should take into account the availability of evidence-based risk-reduction strategies and the probability of developing a malignancy during childhood. Where risk-reduction strategies are available or cancer predominantly develops in childhood, ASCO believes that the scope of parental authority encompasses the right to decide for or against testing. In the absence of increased risk of a childhood malignancy, ASCO recommends delaying genetic testing until an individual is of sufficient age to make an informed decision regarding such tests. As in other areas of pediatric care, the clinical cancer genetics professional should be an advocate for the best interests of the child. Counseling About Medical Management After Testing: ASCO recommends that oncologists include in pre- and post-test counseling the discussion of possible risks and benefits of cancer early-detection and prevention modalities, some of which have presumed but unproven efficacy for individuals at increased hereditary risk of cancer. Regulation of Genetic Testing: ASCO recommends strengthening regulatory oversight of laboratories that provide clinical cancer predisposition tests. These quality assurance mechanisms should include oversight of the reagents used in genetic testing, interlaboratory comparisons of reference samples, standardization of laboratory genetic test reports, and proficiency testing. Protection From Insurance and Employment Discrimination: ASCO supports establishing a federal law to prohibit discrimination by health insurance providers and employers on the basis of an individual's inherited susceptibility to cancer. Protections against genetic discrimination should apply to those with group coverage, those with individual health insurance policies, and the uninsured. Coverage of Services: ASCO supports efforts to ensure that all individuals at significantly increased risk of hereditary cancer have access to appropriate genetic counseling, testing, screening, surveillance, and all related medical and surgical interventions, which should be covered without penalty by public and private third-party payers. Confidentiality and Communication of Familial Risk: ASCO recommends that providers make concerted efforts to protect the confidentiality of genetic information. However, they should remind patients of the importance of communicating test results to family members, as part of pretest counseling and informed consent discussions. ASCO believes that the cancer care provider's obligations (if any) to at-risk relatives are best fulfilled by communication of familial risk to the person undergoing testing, emphasizing the importance of sharing this information with family members so that they may also benefit. Educational Opportunities in Genetics: ASCO is committed to continuing to provide educational opportunities for physicians and other health care providers regarding the methods of cancer risk assessment, the clinical characteristics of hereditary cancer susceptibility syndromes, and the range of issues related to genetic testing, including pre- and post-test genetic counseling, and risk management, so that health professionals may responsibly integrate the care of persons at increased genetic risk of cancer into the practice of clinical and preventive oncology. Special Issues Relating to Genetic Research on Human Tissues:ASCO recommends that all researchers proposing to use or store human biologic specimens for genetic studies should consult either the responsible institutional review board (IRB) or a comparable body specifically constituted to assess human tissue research, to determine the requirements for protection specific to the study under consideration. This consultation should take place before the project is initiated. The determination of the need for informed consent or authorization in such studies should depend on whether the research involves tests for genetic markers of known clinical significance and whether research data will be linked to protected health information, as well as other considerations specific to the study proposed. Special attention should also be paid to 1) whether future research findings will be disclosed to the research participants, 2) whether future contact of participants is planned, 3) whether and how protected health information about the tissue donors will be stored, and what will happen to study specimens after the trial ends. In addition, ASCO affirms the right of people contributing tissue to a databank to rescind their permission, in accordance with federal privacy regulations.


MR of xanthogranuloma of the choroid plexus.
We present a case of a xanthogranuloma of the lateral ventricle choroid plexus in association with focal areas of abnormal T2 signal in the tegmentum of the pons as well as within the middle cerebellar peduncles. The characteristic MR appearance of this rare entity is described along with a pathologic basis suggesting an association with posterior fossa lesions.


Benralizumab for the treatment of asthma.
Benralizumab is a humanized monoclonal antibody directed at the a subunit of the interleukin-5 receptor (IL-5R) that is under clinical development. The binding of benralizumab with the alpha chain of IL-5R results in inhibition of hetero-oligomerization of alpha and beta subunits and thus no signal transduction occurs. Consequently, this inhibition prevents proliferation of eosinophils and basophils and the cascade of events following it. Several pivotal trials have documented that benralizumab reduces asthma exacerbation rates with a significant increase in time to the next exacerbation, statistically improves prebronchodilator forced expiratory volume in 1 second (FEV1) and disease-specific health-related quality of life, and is well tolerated in patients with severe asthma and blood eosinophil counts greater than or equal to 150 cells/mcL.


A preliminary study of the epidemiological factors related to honey bee colony loss in Spain.
In recent years, a worldwide decline in the Apis mellifera populations has been detected in many regions, including Spain. This decline is thought to be related to the effects of pathogens or pesticides, although to what extent these factors are implicated is still not clear. In this study, we estimated the prevalence of honey bee colony depopulation symptoms in a random selected sample (n = 61) and we explored the implication of different pathogens, pesticides and the flora visited in the area under study. The prevalence of colony depopulation symptoms in the professional apiaries studied was 67.2% [95% confidence interval (CI) = 54.6-79.8; P < 0.0001]. The most prevalent pathogen found in the worker honey bee samples was Nosema ceranae[65.6%; 95% CI = 52.8-78.3; P < 0.0001], followed by Varroa destructor[32.7%; 95% CI = 20.2-45.4; P < 0.0001] and 97.5% of the colonies infected by N. ceranae were unhealthy (depopulated). Co-infection by V. destructor and N. ceranae was evident in 22.9% (95% CI = 11.6-34.3; P < 0.0001) of the samples and only in unhealthy colonies. Of the 40 pesticides studied, only nine were detected in 49% of the stored pollen samples analysed. Fipronil was detected in only three of 61 stored pollen samples and imidacloprid was not detected in any. Acaricides like fluvalinate, and chlorfenvinphos used to control Varroa mite were the most predominant residues in the stored pollen, probably as a result of their application in homemade formulae. None of the pesticides identified were statistically associated to colony depopulated. This preliminary study of epidemiological factors suggests that N. ceranae is a key factor in the colony losses detected over recent years in Spain. However, more detailed studies that permit subgroup analyses will be necessary to contrast these findings.


Development of molecularly imprinted polymer nanoarrays of N-acryloyl-2-mercaptobenzamide on a silver electrode for ultratrace sensing of uracil and 5-fluorouracil.
The present work describes a new, simple and easy method for the generation of novel molecularly imprinted polymer-based nanoarrays with uracil and 5-fluorouracil as template(s) on the surface of a silver electrode. The procedure involved electrochemical etching of silver-wire to develop nanopores on its tip. In these nanopores, a prepolymer mixture with template(s) was filled-in via spin coating and subjected to free radical thermal polymerization. The bulk polymer and polymer film characteristics were investigated using Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, scanning electron microscopy, and atomic force microscopy. The prepolymerization complex stoichiometry involved one template molecule and two molecules of the N-acryloyl-2-mercaptobenzamide functional monomer. The molecular structure of this complex was thermodynamically optimized via density functional theory at the MP2/6-31+G(d,p) level. The nanoarrays, vertically tethered imprinted polymer brushes with embedded carbon nanotubes, helped enhancing the surface area of the electrode. This drastically facilitated unhindered vertical diffusion with selective binding of uracil and 5-fluorouracil and their sensitive analysis using differential pulse anodic stripping voltammetry, with detection limits as low as 0.50 and 0.33 ng mL-1 (S/N = 3), respectively. The proposed nanoscale electro-chemical sensor was also validated with the complex matrices of blood plasma and pharmaceutics which assured reliable results, without any matrix effect, cross-reactivity, and false-positives. The large therapeutic range of the test analyte (uracil 1.49-278.76 ng mL-1, 5-fluorouracil 1.33-401.15 ng mL-1), demonstrating a perfect linearity (R2 = 0.98) with the improved voltammetric response, merits special significance for the primitive diagnosis of several chronic diseases, in clinical settings, without any sample pretreatment.


A Simpler Machine Learning Model for Acute Kidney Injury Risk Stratification in Hospitalized Patients.
Background: Hospitalization-associated acute kidney injury (AKI), affecting one-in-five inpatients, is associated with increased mortality and major adverse cardiac/kidney endpoints. Early AKI risk stratification may enable closer monitoring and prevention. Given the complexity and resource utilization of existing machine learning models, we aimed to develop a simpler prediction model. Methods: Models were trained and validated to predict risk of AKI using electronic health record (EHR) data available at 24 h of inpatient admission. Input variables included demographics, laboratory values, medications, and comorbidities. Missing values were imputed using multiple imputation by chained equations. Results: 26,410 of 209,300 (12.6%) inpatients developed AKI during admission between 13 July 2012 and 11 July 2018. The area under the receiver operating characteristic curve (AUROC) was 0.86 for Random Forest and 0.85 for LASSO. Based on Youden's Index, a probability cutoff of >0.15 provided sensitivity and specificity of 0.80 and 0.79, respectively. AKI risk could be successfully predicted in 91% patients who required dialysis. The model predicted AKI an average of 2.3 days before it developed. Conclusions: The proposed simpler machine learning model utilizing data available at 24 h of admission is promising for early AKI risk stratification. It requires external validation and evaluation of effects of risk prediction on clinician behavior and patient outcomes.


Neuropsychiatric Manifestations in Systemic Lupus Erythematosus Patients at a Tertiary Hospital in Peru.
Systemic lupus erythematosus is a prevalent autoimmune disease that affects multiples systems, exerting its most incapacitating and life-threatening impact through neuropsychiatric involvement. According to the American College of Rheumatology (ACR), 19 neuropsychiatric syndromes types of SLE are classified into categories encompassing the central and peripheral nervous systems. This study aimed to investigate the frequency of neuropsychiatric manifestations in systemic lupus erythematosus patients admitted to Hospital Cayetano Heredia in Lima, Peru, between 2008 and 2019. A retrospective observational study was conducted, entailing the review of 240 medical records of patients diagnosed with systemic lupus erythematosus during the specified period, based on the Systemic Lupus International Collaborating Clinics (SLICC) 2012 criteria. Among these records, 55 patients presented neuropsychiatric systemic lupus erythematosus (NPSLE). Data were collected using standardized form and entered into Microsoft Excel 2019 database. Statistical analysis was performed using Stata v16. The frequency of neuropsychiatric compromise in systemic lupus erythematosus patients was found to be 22.91%. Among the 55 systemic lupus erythematosus patients, 40 demonstrated involvement of the central nervous system (72.72%), 2 exhibited involvement of the peripheral nervous system (3.63%), and 13 displayed involvement in both the central nervous system and peripheral nervous system (23.63%). The most prevalent psychiatric disorder observed was a major depressive disorder, with a prevalence rate of 30.9%. The study revealed a frequency of 22.91% for neuropsychiatric involvement in systemic lupus erythematosuspatients at Cayetano Heredia Hospital between 2008 and 2019, with central nervous system manifestations prevailing. Furthermore, the findings suggest that NPSLE commonly manifested after the diagnosis of systemic lupus erythematosus.


Novel and disappearing climates in the global surface ocean from 1800 to 2100.
Marine ecosystems are experiencing unprecedented warming and acidification caused by anthropogenic carbon dioxide. For the global sea surface, we quantified the degree that present climates are disappearing and novel climates (without recent analogs) are emerging, spanning from 1800 through different emission scenarios to 2100. We quantified the sea surface environment based on model estimates of carbonate chemistry and temperature. Between 1800 and 2000, no gridpoints on the ocean surface were estimated to have experienced an extreme degree of global disappearance or novelty. In other words, the majority of environmental shifts since 1800 were not novel, which is consistent with evidence that marine species have been able to track shifting environments via dispersal. However, between 2000 and 2100 under Representative Concentrations Pathway (RCP) 4.5 and 8.5 projections, 10-82% of the surface ocean is estimated to experience an extreme degree of global novelty. Additionally, 35-95% of the surface ocean is estimated to experience an extreme degree of global disappearance. These upward estimates of climate novelty and disappearance are larger than those predicted for terrestrial systems. Without mitigation, many species will face rapidly disappearing or novel climates that cannot be outpaced by dispersal and may require evolutionary adaptation to keep pace.


Computerized quantification of pain drawings.
Background and aims Using a computer algorithm to quantify pain drawings could be useful, especially when large numbers of drawings need to be assessed. Whilst informal visual assessment of pain drawings can give clinicians a quick impression of the extent of pain and its location, formal quantification of pain drawings by computer for research purposes is not necessarily trivial. The current study compared seven different approaches to quantification in a large sample of clinical spinal pain drawings. Methods A large number (n = 55,720) of pain drawings were extracted from the SpineData database, a clinical registry of spinal pain patients in the Region of Southern Denmark. Drawings were analyzed both as pixel (raster) and vector based images, with different approaches based on the raw pain drawing, simple encircling polygons, convex-hull encircling polygons and discrete anatomical regions. Data were analyzed using principal component analysis, correlation and linear regression, as well as informal visual inspection of outlier pain drawings. Results Eighty-one percent of the variance could be explained by the first principal component, which we interpreted as the true score variance, i.e. the variance attributable to differences in pain area between individuals. The second principal component explained 10% of the variance and was loaded differentially by polygon-based methods and non-polygon-based methods. Correlations between the different approaches ranged from 0.66 to 1.00. Some approaches correlated so strongly as to be interchangeable, others tended to bias area estimates significantly. Visual inspection of outlier pain drawing indicated that when the different approaches to quantification yielded different results, characteristic patterns could be identified in the style and patterns of those pain drawings. Conclusions The different approaches reflected the same underlying construct (pain area), but could not be relied upon to produce the same area estimates and were affected by the interaction between drawing style and quantification approach. To some extend, the "correct" choice of quantification method is specific to and dictated by the style of each pain drawing. A differentiated approach is required in which the results of quantification and the drawing style are considered in combination. We provide suggestions for such differentiated approaches taking into account the nature of the drawing data (raster vs. vector) and the method of analysis (partly vs completely automated). Implications The chosen method of quantifying pain drawings in combination with the drawing style of the individual patient, can impact the resulting area estimate to a significant degree. These issues should be considered before undertaking computerized area estimation of pain drawings.


Prognostic utility of the pericoronary fat attenuation index in patients with takotsubo cardiomyopathy.
The etiology of takotsubo cardiomyopathy (TCM) remains poorly understood and no optimal management strategy has been established. Identification of features associated with poor outcomes may improve the prognosis of patients with TCM. We aimed to identify the predictors of poor prognosis in patients with TCM using coronary computed tomography angiography (CCTA). We enrolled consecutive patients with TCM who underwent CCTA during the acute disease phase. The pericoronary fat attenuation index (FAI) of adipose tissue was obtained from CCTA images. Major adverse cardiac and cerebrovascular events (MACCE) were defined as all-cause death, non-fatal myocardial infarction, stroke, rehospitalization due to congestive heart failure, and TCM recurrence. The relationships between patient characteristics and CCTA findings were compared between patients with and without MACCE. A total of 52 patients were included (10 men [19.2%]; mean age, 71 years). After a median follow-up of 23 months, MACCE had developed in 10 patients (19.2%). There were significant differences in clinical characteristics [including the three-vessel mean FAI (FAI-mean)] between patients with and without MACCE. Univariate Cox regression analyses showed that FAI-mean ≥ -68.94 Hounsfield units (cut-off value derived from receiver operating characteristic curve analysis) (hazard ratio [HR], 13.52; 95% confidence interval [CI], 1.705-107.2; p = 0.014) and NT-proBNP (HR, 1.000; 95% CI, 1.000-1.000; p = 0.022) were significant predictors of MACCE. FAI-mean ≥ -68.94 HU was significantly associated with MACCE (chi-squared statistic = 10.3, p = 0.001). In patients with TCM, a higher FAI-mean was significantly associated with poorer outcomes independent of the conventional risk factors.


Clitoria ternatea L. as a Potential High Quality Forage Legume.
Samples of Clitoria ternatea L. (Cunhã) were harvested at 35, 50, 70, and 90 d after a uniformity harvest in a field study designed as a completely randomized design with a total of 18 experimental plots. The dry matter yield of the whole plant was separated quantitatively into leaves, stems, and pods at each harvesting age. Chemical analyses and in vitro gas production kinetics were performed to assess the quality of the plant parts. Yields, chemical composition, and estimates of gas production parameters were analyzed by fitting a mixed statistical model with two types of covariance structures as follows: variance components and an unrestricted structure with heterogeneous variances. Fast and slow gas yielding pools were detected for both leaves and stems, but only a single pool was detected for pods. The homoscedasticity assumption was more likely for all variables, except for some parameters of the gas production kinetics of leaves and stems. There was no presence of typical pods at 35 and 50 d. In the leaves, the fibrous fractions were affected, whereas the non-fibrous fractions were unaffected by the harvesting age. The harvesting age affected the majority of the chemical constituents and gas kinetic parameters related to the stems. The leaves of this legume were the least affected part by the aging process.


Pulmonary arterial hypertension: a comparison between children and adults.
The characteristics of pulmonary arterial hypertension (PAH), including pathology, symptoms, diagnosis and treatment are reviewed in children and adults. The histopathology seen in adults is also observed in children, although children have more medial hypertrophy at presentation. Both populations have vascular and endothelial dysfunction. Several unique disease states are present in children, as lung growth abnormalities contribute to pulmonary hypertension. Although both children and adults present at diagnosis with elevations in pulmonary vascular resistance and pulmonary artery pressure, children have less heart failure. Dyspnoea on exertion is the most frequent symptom in children and adults with PAH, but heart failure with oedema occurs more frequently in adults. However, in idiopathic PAH, syncope is more common in children. Haemodynamic assessment remains the gold standard for diagnosis, but the definition of vasoreactivity in adults may not apply to young children. Targeted PAH therapies approved for adults are associated with clinically meaningful effects in paediatric observational studies; children now survive as long as adults with current treatment guidelines. In conclusion, there are more similarities than differences in the characteristics of PAH in children and adults, resulting in guidelines recommending similar diagnostic and therapeutic algorithms in children (based on expert opinion) and adults (evidence-based).


NOX4 Regulates CCR2 and CCL2 mRNA Stability in Alcoholic Liver Disease.
Recruitment of inflammatory cells is a major feature of alcoholic liver injury however; the signals and cellular sources regulating this are not well defined. C-C chemokine receptor type 2 (CCR2) is expressed by active hepatic stellate cells (HSC) and is a key monocyte recruitment signal. Activated HSC are also important sources of hydrogen peroxide resulting from the activation of NADPH oxidase 4 (NOX4). As the role of this NOX in early alcoholic liver injury has not been addressed, we studied NOX4-mediated regulation of CCR2/CCL2 mRNA stability. NOX4 mRNA was significantly induced in patients with alcoholic liver injury, and was co-localized with αSMA-expressing activated HSC. We generated HSC-specific NOX4 KO mice and these were pair-fed on alcohol diet. Lipid peroxidation have not changed significantly however, the expression of CCR2, CCL2, Ly6C, TNFα, and IL-6 was significantly reduced in NOX4HSCKO compared to fl/fl mice. NOX4 promoter was induced in HSC by acetaldehyde treatment, and NOX4 has significantly increased mRNA half-life of CCR2 and CCL2 in conjunction with Ser221 phosphorylation and cytoplasmic shuttling of HuR. In conclusion, NOX4 is induced in early alcoholic liver injury and regulates CCR2/CCL2 mRNA stability thereby promoting recruitment of inflammatory cells and production of proinflammatory cytokines.


Mitochondrial DNA markers reveal high genetic diversity but low genetic differentiation in the black fly Simulium tani Takaoka & Davies along an elevational gradient in Malaysia.
The population genetic structure of Simulium tani was inferred from mitochondria-encoded sequences of cytochrome c oxidase subunits I (COI) and II (COII) along an elevational gradient in Cameron Highlands, Malaysia. A statistical parsimony network of 71 individuals revealed 71 haplotypes in the COI gene and 43 haplotypes in the COII gene; the concatenated sequences of the COI and COII genes revealed 71 haplotypes. High levels of genetic diversity but low levels of genetic differentiation were observed among populations of S. tani at five elevations. The degree of genetic diversity, however, was not in accordance with an altitudinal gradient, and a Mantel test indicated that elevation did not have a limiting effect on gene flow. No ancestral haplotype of S. tani was found among the populations. Pupae with unique structural characters at the highest elevation showed a tendency to form their own haplotype cluster, as revealed by the COII gene. Tajima's D, Fu's Fs, and mismatch distribution tests revealed population expansion of S. tani in Cameron Highlands. A strong correlation was found between nucleotide diversity and the levels of dissolved oxygen in the streams where S. tani was collected.


Cell biology of osteochondromas: bone morphogenic protein signalling and heparan sulphates.
Frequent benign outgrowths from bone known as osteochondromas, exhibiting typical endochondral ossification, are reported from single to multiple lesions. Characterised by a high incidence of osteochondromas and skeletal deformities, multiple hereditary exostoses (MHE) is the most common inherited musculoskeletal condition. While factors for severity remain unknown, mutations in exostosin 1 and exostosin 2 genes, encoding glycosyltransferases involved in the biosynthesis of ubiquitously expressed heparan sulphate (HS) chains, are associated with MHE. HS-binding bone morphogenetic proteins (BMPs) are multifunctional proteins involved in the morphogenesis of bone and cartilage. HS and HS proteoglycans are involved in BMP-mediated morphogenesis by regulating their gradient formation and activity. Mutations in exostosin genes disturb HS biosynthesis, subsequently affecting its functional role in the regulation of signalling pathways. As BMPs are the primordial morphogens for bone development, we propose the hypothesis that BMP signalling may be critical in osteochondromas. For this reason, the outcomes of exostosin mutations on HS biosynthesis and interactions within osteochondromas and MHE are reviewed. Since BMPs are HS binding proteins, the interactions of HS with the BMP signalling pathway are discussed. The impact of mouse models in the quest to better understand the cell biology of osteochondromas is discussed. Several challenges and questions still remain and further investigations are needed to explore new approaches for better understanding of the pathogenesis of osteochondromas.


Is Burning Mouth Syndrome Associated with Extraoral Dryness? A Systematic Review.
Burning mouth syndrome (BMS) is characterized by a persistent intraoral burning sensation, often experienced by postmenopausal women. The etiology of BMS remains partially understood, and consequently, treatments remain suboptimal. Extraoral manifestations of BMS, such as extraoral dryness, are less studied. However, it has been suggested that the identification of the frequency and patterns of extraoral dryness and potential underlying mechanisms are essential to optimize treatment strategies and reduce the burden of disease. Therefore, we conducted this systematic review to provide existing evidence about extraoral dryness in BMS. The guidelines for the conduction and reporting of systematic reviews were followed. An electronic search was conducted in four major databases-PubMed, Web of Science, COCHRANE Library, and EBSCOhost-and the grey literature was assessed through Google Scholar. From each included article, information on extraoral dryness in BMS was extracted, and odds ratios were calculated for extraoral dryness among BMS patients compared with non-BMS controls. The findings demonstrated higher odds of the prevalence of extraoral dryness in BMS, which was found to a high degree in the lips, eyes, skin, and genitalia. The pattern of spread and locations of extraoral dryness propose a potential central mechanism. Based on our findings, we encourage the standardization of the assessment, recording, and reporting of the extraoral characteristics of BMS, including extraoral dryness, which can lead to better management strategies and enhance the quality of life of the affected patients.


A randomized trial of a lay person-led self-management group intervention for back pain patients in primary care.
Randomized, controlled trial. To evaluate a four-session self-management group intervention for patients with pain in primary care, led by trained lay persons with back pain. The intervention was designed to reduce patient worries, encourage self-care, and reduce activity limitations. Randomized trials of educational interventions suggest that activating interventions may improve back pain outcomes. Expert opinion increasingly regards effective self-management of back pain as important in achieving good outcomes. In this study, an educational intervention designed to activate patients and support effective self-management was evaluated. Six to 8 weeks after a primary care visit for back pain, patients were invited to participate in an educational program to improve back pain self-management. Those showing interest by returning a brief questionnaire became eligible for the study. Participants (n = 255) randomly were assigned to either a self-management group intervention or to a usual care control group. The effect of the intervention, relative to usual care, was assessed 3, 6, and 12 months after randomization, controlling for baseline values. The intervention consisted of a four-session group applying problem-solving techniques to back pain self-management, supplemented by educational materials (book and videos) supporting active management of back pain. The groups were led by lay persons trained to implement a fully structured group protocol. The control group received usual care, supplemented by a book on back pain care. Participants randomly assigned to the self-management groups reported significantly less worry about back pain and expressed more confidence in self-care. Roland Disability Questionnaire Scores were significantly lower among participants in the self-management groups relative to the usual care controls at 6 months (P = 0.007), and this difference was sustained at 12 months at borderline significance levels (P = 0.09). Among self-management group participants, 48% showed a 50% or greater reduction in Roland Disability Questionnaire Score at 6 months, compared with 33% among the usual care controls. Self-management groups led by trained lay persons following a structured protocol were more effective than usual care in reducing worries, producing positive attitudes toward self-care, and reducing activity limitations among patients with back pain in primary care.


How prepared are students for the various transitions in their medical studies? An Australian university pilot study.
This article was migrated. The article was marked as recommended. Becoming a doctor involves a series of transitions that require medical students to be equipped with the appropriate knowledge, skills, confidence and professional approach at each step. This pilot cross-sectional study canvassed five cohorts immediately after completing Years 1-5 in a five-year undergraduate medical program (Gold Coast, Australia) regarding their preparedness for the next year. The survey, an amalgamation of two validated inventories, was tailored for each year group to include the expected competencies in five areas. Despite a low response, those who did participate provided valuable information regarding their competence and confidence in terms of their interpersonal and intrapersonal skills, their clinical skills, their ability to apply their theoretical knowledge and investigations. Time management and balancing work and their studies were some areas in which support might be needed. Generally, all student felt comfortable with the communication and physical examination skills but up to half of some of the more senior students were not confident towards dealing with a violent patient and about 20% did not feel at ease communicating and assessing a patient with a mental health issue. Students identified two other areas that requiring curriculum interventions: Working with patients who might be using non-allopathic medications and calculating drug doses. As both impact on patient outcomes, a follow-up study is required. Different recruitment strategies need to be investigated.


Is serum protein electrophoresis useful in separating the "high risk group" in patients with colonic polyps?
Adenomas have the highest potential or clinical value from among colonic polyps of developing into adenocarcinoma. The aims of this paper are: to establish criteria to identify the high risk group of patients in a group of patients with colonic polyps, to work out a simple scheme for follow-up care after endoscopic polypectomy, and to establish indications for surgery. The usefulness of determination of electrophoresis of serum proteins has been specially analysed to detect early development of malignant growths in patients with colonic polyps regarding alfa-1/alfa-2 and alfa/beta. 67 cases - 21 women, 46 men were tested. Follow-up endoscopy with the electrophoresis was performed after 6 weeks, 6 and 12 months after polypectomy. 97 polyps were resected with endoscopy in 67 patients. 38 patients (39.17%), those constituting the high risk group, were selected. Included were all polyps with grade II and III of cellular differentiation. 1) alfa-1/alfa-2 and alfa/beta is a helpful test in identifying the high risk group among patients with colonic polyps and it can be used as a screening test, 2) the determination of beta-2-macroglobuline is not useful in the diagnosis of this group of patients, 3) the electrophoresis of proteins should be the first test to perform on patients with colonic polyps. The relation of electrophoresis to endoscopic polypectomy aids evaluations of patients specially predisposed to malignant.


Geographical Variation in Oral and Oropharynx Cancer Mortality in Brazil: A Bayesian Approach.
Recent studies have shown a high number of deaths from oral and oropharyngeal cancer worldwide, Brazil included. For this study, the deaths data (ICD-10, chapter II, categories C00 to C14) was obtained from Mortality Information System (SIM) and standardized by gender and population for each of the 554 Microregions of Brazil. The raw mortality rates were adopted as the standard and compared to the application of smoothing by the Bayesian model. In order to describe the geographical pattern of the occurrence of oral cancer, thematic maps were constructed, based on the distributions of mortality rates for Microregions and gender. Results: There were 7882 deaths registered due to oral and oropharyngeal cancer in Brazil, of which 6291 (79.81%) were male and 1591 (20.19%) female. The Empirical Bayesian Model presented greater scattering with mosaic appearance throughout the country, depicting high rates in Southeast and South regions interpolated with geographic voids of low rates in Midwest and North regions. For males, it was possible to identify expressive clusters in the Southeast and South regions. Conclusion: The Empirical Bayesian Model allowed an alternative interpretation of the oral and oropharynx cancer mortality mapping in Brazil.


Fatal peritonitis following IUD-associated salpingitis.
Previous reports have implicated the Dalkon shield intrauterine device (IUD) in septic second trimester abortion and maternal death from sepsis. In the case reported here, Fusobacterium necrophorum, a rarely pathogenic vaginal anaerobe, gained access to the uterus in a woman wearing a Dalkon shield and caused acute parametritis, overwhelming peritonitis, systemic sepsis, and death. It is well known that IUDs can contribute to the development of serious pelvic infections, and in this case it is possible that the Dalkon shield was the cause of the ascending infection into the uterus.


Trauma death: views of the public and trauma professionals on death and dying from injuries.
To determine the values and preferences of the general public and trauma professionals regarding end-of-life care due to injury so as to inform practice guidelines. Surveys of the general public sampled by random-digit dialing between June 6, 2005, and July 5, 2005, and of a convenience sample of trauma professionals during fall 2005 in the United States were conducted regarding preferences for care in the prehospital, emergency, and critical care settings. Responses to the survey questions. Most of the public and trauma professionals would prefer palliative care when doctors determine that aggressive critical care would not be beneficial in saving their lives. During resuscitation of an injured loved one, 51.9% of the public and 62.7% of the professionals would prefer to be in the emergency department treatment room. Most of the public believes that patients should have the right to demand care not recommended by their physicians. Most of both groups trust a doctor's decision to withdraw treatment when futility is determined. More of the public (57.4%) than the professionals (19.5%) believe that divine intervention could save a person when physicians believe treatment is futile. Other findings suggest further important insights. The results pose challenges that will require societal discourse to determine the best practice. Resolutions will need to be included in educational curricula and incorporated into practice to ensure that dying trauma victims and their families receive quality end-of-life care.


Evaluation of the Impact of Oral Health Education on Oral Hygiene Knowledge and Plaque Control of School-going Children in the City of Amritsar.
The present study aims to evaluate the impact of oral health education on oral hygiene knowledge and plaque control of school-going children in the city of Amritsar. The study was carried out for 6 weeks and included four groups of schoolchildren of 10-12 years of age. Children were randomly selected and assigned into one of the four groups - Group I (verbal communication), Group II (verbal communication and self-educational pamphlets), Group III (audiovisual aids and verbal communication), and Group IV (control group). Oral health education was assessed by getting a questionnaire filled by children and plaque scores was recorded using Silness and Loe plaque index before and after the study. The data were then compared and analyzed using SPSS 16 software manufactured by IBM. Differences in knowledge gain after the dental health education were statistically significant between all the groups, except between Group II and Group III in which the difference was not found to be significant. Group III showed the highest decrease in plaque score followed by Group II. There was a significant difference in reduction in plaque scores between all the groups, except between the Groups II and III. Both methods, i.e., pamphlets and audiovisual aids when used along with oral lectures, are equally effective in improving the knowledge and plaque scores in children.


In vitro antibacterial and antifungal activities of different solvent extracted samples from the stem of Euphorbia heliscopia.
This paper presents the anti-microbial potentials of methanol, ethyl acetate, n-hexane, butanol and water extracted samples from the stem of Euphorbia heliscopia against S. aureus (Gram positive), B. subtilis (Gram positive), P. aeruginosa (Gram negative), K. pneumonia (Gram negative), E. coli (Gram negative), C. albicans (fungal specie) by discs diffusion susceptibility assay using 0.5 and 1mg disc-1 concentrations. Our results showed that all the extracted samples from the stem of E. heliscopia exhibited varying degree of antimicrobial activity. Ethyl acetate extracted samples measured maximum activity against the studies microbial species followed by the n-butanol and crude methanolic extract. n-hexane extracted samples inhibited the growth of all microbial species except P. aeruginosa and E. coli at lower concentration. Aqueous fractions showed inhibitory activity against B. subtilis, K. pneumonia and C. albicans. The most susceptible gram positive bacteria were S. aureus while B. subtilis was the most resistant one. Among Gram negative bacteria, P. aeruginosa showed more susceptibility while K. pneumonia was resistant.


Hereditary canine spinal muscular atrophy is phenotypically similar but molecularly distinct from human spinal muscular atrophy.
Hereditary canine spinal muscular atrophy (HCSMA) is an autosomal dominant motor neuron disease that is similar in pathology and clinical presentation to various forms of human motor neuron disease. We have tested the hypothesis that the canine survival motor neuron (SMN) gene is responsible for HCSMA by genetic and molecular analysis of a colony of mixed breed dogs, all descended from a single affected individual. We cloned the canine SMN gene and determined the DNA sequence in an affected and an unaffected dog. We found no germline mutations in the SMN gene of the affected individual. Using conventional linkage analysis with canine-specific microsatellite repeat markers we screened the canine genome and identified a single linkage group likely to contain the HCSMA gene. Analysis with a panel of canine/rodent hybrid cell lines revealed that the SMN gene did not map to the same chromosome as the HCSMA linkage group. Collectively these results suggest that the molecular basis for HCSMA is distinct from that of phenotypically similar human disorders caused by inherited mutations in the SMN gene. This further suggests that additional studies on the molecular nature of HCSMA may reveal an unknown element of the molecular pathway leading to motor neuron disease.


Responsive mesoporous silica nanoparticles for sensing of hydrogen peroxide and simultaneous treatment toward heart failure.
Chronic heart failure is often characterized by the elevated amounts of reactive oxygen species such as hydrogen peroxide (H2O2) in the heart. Thus, it is of importance that selective release of therapeutic drugs occurs at the heart failure site to maximize therapeutic effects. In this work, functional mesoporous silica nanoparticles (MSNPs) were developed for detection of H2O2, selective drug release and controlled treatment toward heart failure. The H2O2-sensitive probe was attached to the surface of the MSNPs, and a therapeutic drug of heart failure, captopril, was loaded within the pores of the MSNPs and retained by the binding of α-cyclodextrin to the probe. H2O2 present in tissue could react with the probe and enable the dissociation of α-cyclodextrin present on the nanoparticle surface, so that captopril could be successfully released along with "turn-on" of the probe fluorescence. In vivo experiments using the KillerRed heart failure transgenic zebrafish model demonstrated that this therapeutic system is physiologically responsive. Captopril-loaded MSNPs showed high therapeutic efficacy, improving the heartbeat rate and cardiac output in zebrafish experiencing acute KillerRed-induced heart failure.


Effects of pen enrichment on leg health of fast and slower-growing broiler chickens.
Pen enrichment for broiler chickens is one of the potential strategies to stimulate locomotion and consequently contribute to better leg health and welfare. This study was designed to evaluate effects of using a plethora of pen enrichments (barrier perches, angular ramps, horizontal platforms, large distance between feed and water and providing live Black Soldier fly larvae in a dustbathing area) on tibia characteristics, locomotion, leg health and home pen behaviour of fast and slower-growing broiler chickens. The experiment was set up as a 2 x 2 factorial arrangement with a total of 840 male broiler chickens in a complete randomized design (7 pens per treatment and 30 chickens per pen) with the following treatments: 1) pen enrichment (enriched pen or non-enriched pen); 2) broiler strain (fast-growing Ross 308 or slower-growing Hubbard JA 757). Home pen behaviour and use of enrichment were observed. At approximately 1400 and 2200 g body weight, two chickens per pen were randomly selected and slaughtered, to investigate tibia morphological, biophysical and mechanical characteristics and leg health. Pen enrichment positively affected tibia biophysical characteristics, e.g., osseous volume (Δ = 1.8 cm3, P = 0.003), total volume (Δ = 1.4 cm3, P = 0.03) and volume fraction (Δ = 0.02%, P = 0.002), in both fast and slower-growing chickens, suggesting that pen enrichment particularly affects ossification and mineralization mechanisms. Accordingly, locomotion and active behaviours were positively influenced by pen enrichment. However, pen enrichment resulted in lower body weight gain in both strains, which might be due to higher activity or lower feed intake as a result of difficulties of crossing the barrier perches. Regarding the strain, slower-growing chickens showed consistently more advanced tibia characteristics and more active behaviour than fast-growing chickens. It can be concluded that pen enrichment may lead to more activity and better bone development in both fast and slower-growing chickens.


A Clinical Care Algorithmic Toolkit for Promoting Screening and Next-Level Assessment of Pediatric Depression and Anxiety in Primary Care.
With a documented shortage in youth mental health services, pediatric primary care (PPC) providers face increased pressure to enhance their capacity to identify and manage common mental health problems among youth, such as anxiety and depression. Because 90% of U.S. youth regularly see a PPC provider, the primary care setting is well positioned to serve as a key access point for early identification, service provision, and connection to mental health services. In the context of task shifting, we evaluated a quality improvement project designed to assist PPC providers in overcoming barriers to practice-wide mental health screening through implementing paper and computer-assisted clinical care algorithms. PPC providers were fairly successful at changing practice to better address mental health concerns when equipped with screening tools that included family mental health histories, next-level actions, and referral options. Task shifting is a promising strategy to enhance mental health services, particularly when guided by computer-assisted algorithms.


Butter Tolerance in Children Allergic to Cow's Milk.
We performed an oral food challenge (OFC) with 10 g of butter (equivalent of 2.9 mL cow's milk) and 25-mL heated cow's milk for 68 children with cow's milk-allergy. Thirty-eight children reacted only to heated cow's milk. Twenty-four children reacted to neither heated milk nor butter. Thirty-eight (86.4%) of 44 patients with positive results to the OFC for heated milk could safely tolerate butter. It is highly likely that even children with cow's milk-allergy who show positive results to an OFC for heated milk can consume butter. The milk-specific IgE value indicative of a negative predictive value of over 95% was 17.8 kUA/L, and patients with low milk-specific IgE values may be able to safely consume butter. Including butter in the diets of patients with milk-allergy after a butter challenge may improve quality of life.


Energy and fructose from beverages sweetened with sugar or high-fructose corn syrup pose a health risk for some people.
Sugar intake in the United States has increased by >40 fold since the American Revolution. The health concerns that have been raised about the amounts of sugar that are in the current diet, primarily as beverages, are the subject of this review. Just less than 50% of the added sugars (sugar and high-fructose corn syrup) are found in soft drinks and fruit drinks. The intake of soft drinks has increased 5-fold between 1950 and 2000. Most meta-analyses have shown that the risk of obesity, diabetes, cardiovascular disease, and metabolic syndrome are related to consumption of beverages sweetened with sugar or high-fructose corn syrup. Calorically sweetened beverage intake has also been related to the risk of nonalcoholic fatty liver disease, and, in men, gout. Calorically sweetened beverages contribute to obesity through their caloric load, and the intake of beverages does not produce a corresponding reduction in the intake of other food, suggesting that beverage calories are "add-on" calories. The increase in plasma triglyceride concentrations by sugar-sweetened beverages can be attributed to fructose rather than glucose in sugar. Several randomized trials of sugar-containing soft drinks versus low-calorie or calorie-free beverages show that either sugar, 50% of which is fructose, or fructose alone increases triglycerides, body weight, visceral adipose tissue, muscle fat, and liver fat. Fructose is metabolized primarily in the liver. When it is taken up by the liver, ATP decreases rapidly as the phosphate is transferred to fructose in a form that makes it easy to convert to lipid precursors. Fructose intake enhances lipogenesis and the production of uric acid. By worsening blood lipids, contributing to obesity, diabetes, fatty liver, and gout, fructose in the amounts currently consumed is hazardous to the health of some people.


In rats breathing from a nonrebreathing system, substitution of desflurane for isoflurane toward the end of anesthesia incompletely restores the time of recovery toward that of desflurane.
The lower solubility of desflurane allows a more rapid emergence from anesthesia than after anesthesia with the more soluble but less expensive anesthetic, isoflurane. Some practitioners use isoflurane for maintenance of anesthesia, crossing over to desflurane later in maintenance in an attempt to combine the cost-effectiveness of isoflurane with the rapid emergence from desflurane. We hypothesized that this maneuver would not accomplish its goals. Twenty-four male Sprague-Dawley rats received 1.2 minimum alveolar anesthetic concentration (MAC) of desflurane for the final 15, 30, or 60 min of a 2-h, 1.2-MAC isoflurane anesthetic in a nonrebreathing anesthesia system. We measured the time from cessation of anesthetic administration to the time each rat righted himself twice. Immediately after righting for the second time, we tested each rat's ability to remain atop a rotating rod (Rota-Rod) for 60 s continuously. Early (righting reflex) and late (Rota-Rod) recovery occurred more rapidly (P < 0.001) after 120 min of anesthesia with desflurane alone than after 120 min of anesthesia with isoflurane alone. A cross-over period of 30 min or longer produced a righting reflex time that did not differ from that found with desflurane alone, but a 15-min cross-over did not. Progressively longer cross-over periods led to proportionally better Rota-Rod performance, but no cross-over duration produced the rapidity of recovery seen with desflurane alone. We concluded that in a nonrebreathing system, switching to desflurane during the last 30 min of anesthesia substantially improved early recovery but produced a much smaller improvement in later recovery. The newer inhaled anesthetics offer the advantage of lower solubility, and thus more rapid emergence from anesthesia, than do the older inhaled anesthetics. However, they can be more expensive to use. This study demonstrates that substituting the newer anesthetic, desflurane, toward the end of anesthesia for an older anesthetic of greater solubility, isoflurane, does not produce recovery comparable to that of desflurane alone. Furthermore, this technique can be more costly than using desflurane throughout anesthesia.


Genotypic characterization of five subspecies of Mycobacterium kansasii.
Different molecular typing methods including restriction fragment length polymorphism (RFLP) analysis with the major polymorphic tandem repeat (MPTR) probe and the IS1652 probe, pulsed-field gel electrophoresis (PFGE), amplified fragment length polymorphism (AFLP) analysis, and PCR restriction analysis of the hsp-65 gene (PRA) were applied to clinical and water isolates of Mycobacterium kansasii. RFLP with the MPTR probe, PRA, PFGE, and AFLP analysis revealed five homogeneous clusters which appeared to be subspecies. RFLP with the MPTR probe and PRA gave patterns specific for each cluster, whereas PFGE and AFLP analysis gave polymorphic patterns. IS1652 was present in two of the five clusters and provided polymorphic patterns for one cluster only. The two IS1652-positive clusters were Accuprobe negative (Accuprobe test; Gen-Probe Inc.), and only two other clusters were Accuprobe positive. A PCR test based on the detection of a species-specific fragment (M. Yang, B.C. Ross, and B. Dwyer, J. Clin. Microbiol. 31:2769-2772, 1993) was positive for all M. kansasii strains. This PCR test is an accurate, rapid, and specific M. kansasii identification test. No subspecies was particularly more virulent, because all clusters contained clinical strains, from AIDS patients and non-AIDS patients, and environmental strains.


[Subclavian steal: transcranial Doppler sonography of the basilar artery].
In 32 patients with high-grade obstruction of the proximal subclavian artery or of the brachiocephalic trunk and complete or incomplete forms of subclavian steal in the ipsilateral vertebral artery, blood flow in the basilar artery was investigated by transcranial Doppler sonography. With complete steal effect in respect of the vertebral artery, we found, contrary to other investigators, in most cases alterations of the flow in the basilar artery even at rest. These alterations are a systolic deceleration of flow velocity or an alternating flow directed towards the arm in systole and towards the brain in diastole. In about 40% of cases blood flow in the basilar artery could not be assessed, either because the depth of investigation reached was too low, or because--especially in cases with systolic deceleration in one vertebral artery--it was impossible to define the origin of the basilar artery.


Low-intensity ultrasound stimulates proteoglycan synthesis in rat chondrocytes by increasing aggrecan gene expression.
We evaluated the effect of low intensity-pulsed ultrasound stimulation on rat chondrocytes in vitro using two different 1.0-MHz ultrasound signals with spatial and temporal average intensities of 50 or 120 mW/cm2. The pulses had a duration of 200 microseconds and were repeated every millisecond, with corresponding average peak-pressure amplitudes of 230 or 360 kPa, respectively. Cells were stimulated one, three, or five times for 10 minutes each day starting the third day after plating. One group of cells was exposed to sham ultrasound as a control. The cultures were evaluated for cell proliferation (by [3H]thymidine incorporation and DNA measurement), steady-state mRNA levels of alpha1(I) and alpha1(II) procollagens and aggrecan (by Northern blotting), and proteoglycan synthesis (by [35S]sulfate incorporation). The results revealed that ultrasound causes increases in the level of aggrecan mRNA (p < 0.05) and in proteoglycan synthesis (p < 0.03) after three and five treatments. Expression of mRNA for alpha1(II) procollagen increased over time, but ultrasound had no stimulatory effect. Expression of mRNA for alpha1(I) procollagen was initially low and remained unchanged with time. Although cell proliferation increased with time in both groups, there was no statistically significant difference between the cultures treated with ultrasound and the controls (p = 0.1). The in vitro results support our previous in vivo findings that low-intensity ultrasound stimulates aggrecan mRNA expression and proteoglycan synthesis by chondrocytes, which may explain the role of ultrasound in advancing endochondral ossification, increasing the mechanical strength of fractures, and facilitating fracture repair.


A review of the definition, influencing factors, and mechanisms of rapid composting of organic waste.
Composting is a traditional method of treating organic waste. A growing number of studies have been focusing on accelerating the process to achieve "rapid composting." However, the specific definition and influencing factors of rapid composting remain unclear. Therefore, we aimed to gather more insight into the features of rapid composting by reviewing the literature concerning organic waste composting published in the Web of Science database in the past 5 years. We selected 1615 sample studies with "composting" as the subject word and analyzed the effective composting time stated in each study. We defined rapid composting within 15 days using the median test and quartile method. Based on this definition, we summarized the influencing factors of "rapid composting," namely materials, reactors, temperature, and microorganisms. Finally, we summarized two mechanisms related to humus formation during organic waste rapid composting: high temperature-promoting maturation and microbial driving mechanisms. This literature review compiled useful references to help promote the development of rapid composting technology and related equipment.


Can the sensitisation to staphylococcal enterotoxin predict the severity of chronic rhinosinusitis?
Evidence is accumulating that Staphylococcus aureus plays an important role as a disease modifier in upper and lower airway disease. We aimed to assess the association of staphylococcal enterotoxins (SEs) with allergic multimorbidity as well as the severity of chronic rhinosinusitis. We retrospectively reviewed the medical records of 97 subjects aged 6 years or older between March 2018 and June 2019 and analysed symptom scores, computed tomography scores, serum IgE levels to SEs, serum total and specific IgE levels to inhalant allergens. To evaluate eosinophilic chronic rhinosinusitis (ECRS), we used refractory ECRS score from the Japanese epidemiological survey. Of the 97 patients enrolled, 29 (29.9%) were non-sensitised, 33 (34.0%) were mono-sensitised, and 35 (36.1%) were poly-sensitised. Sensitisation to SEs was closely associated with poly-sensitisation to inhalant allergens. SE-sensitised participants had higher median values for total and specific IgE levels to inhalant allergens than did non-SE-sensitised participants. SE sensitisation was associated with allergic multimorbidity and severe allergic diseases, such as ECRS. This preliminary study suggested that sensitisation to SEs may play a role in the initiation of type-2 inflammatory responses, such as allergic rhinitis, ECRS, and allergic multimorbidity. Furthermore, sensitisation to SEs correlated with the severity of ECRS.


Trends and outcomes of treatment for primary rhegmatogenous retinal detachment: a 9-year nationwide population-based study.
To determine the trends and outcomes for treating primary rhegmatogenous retinal detachment (RRD) in a nationwide population-based study in Taiwan. We collected admission data during the period of 1997-2005, from the Taiwan National Health Insurance Research Database, a source that covers over 96% of Taiwan's 23 million citizens. Totally 28 911 patients with a first-time admission diagnosis of RRD (ICD-9-CM codes 361 to 361.07) and undergoing surgical treatment (scleral buckling (SB), pars plana vitrectomy (PPV), or their combination) were identified. The utilized operation type, 180-day readmission rate for recurrent retinal detachment, length of hospital stay, and admission charge were obtained. Contingency table/chi (2) test and t-test were employed for the statistical analysis. Primary PPV (with or without SB) was a primary procedure in 47.3% of cases in 1997. This rate rose significantly to 61.2% in 2005. A significant decrease in the total 180-day readmission rate occurred from 18.95% in 1997 to 13.81% in 2005. These rates also significantly decreased for each surgical modality (from 16.30 to 11.38% for SB, from 21.29 to 14.69% for PPV, and from 22.99 to 16.55% for PPV+SB). The length of hospital stay decreased for each surgical modality between 1997 and 2005. There was a significant trend towards more frequently employing primary PPV (with or without SB) for the management of primary RRD. In addition, significant improvements in the primary success rates were shown for each surgical modality group and for total samples between 1997 and 2005.