Transcriptomic analysis of mechanism of melanoma cell death induced by photothermal therapy.
Melanoma is a malignancy with poor prognosis. Its incidence rate has been on the rise and it poses high health and economic challenges to different populations. Photothermal therapy (PTT) served as an effective local therapy in treating various tumors, particularly cutaneous carcinoma like melanoma. To fully understand the mechanisms of tumor cell death induced by PTT, we investigated gene expression and immune cells compositions of B16-F10 tumors after PTT treatment. A total of 256 differentially expressed genes (DEGs) were identified, with 215 being downregulated and 41 upregulated by PTT. Functional annotation showed that most DEGs involved in immune response and inflammatory response. Immune cells compositions inference revealed changes in many immune cells including regulatory T cells, M2 macrophage and B cells after PTT treatment. Our results help delineate the mechanism of cell death at the transcriptional level triggered by non-invasive PTT treatment of melanoma without exogenous light absorbing agents.


Hepatitis C in HIV-positive patients--treatment and liver disease outcomes.
Many human immunodeficiency virus (HIV) infected persons are coinfected with hepatitis C virus (HCV) and with the use of highly active antiretroviral therapy, liver disease from HCV has become an important cause of morbidity and mortality. The current guidelines recommend that human immunodeficiency virus and HCV coinfected patients be evaluated and treated for HCV if there are no major contraindications to treatment. Coinfected patients treated with pegylated interferon-a and ribavirin have sustained virologic responses (SVRs) of 27% to 40% which for a variety of reasons are lower than those reported in HCV mono-infected patients. Understanding that most patients will not achieve SVRs, strategies to evaluate for the role of maintenance interferon in delaying complications of liver disease are being evaluated. In patients who have failed prior treatment, cannot tolerate treatment, or who have contraindications to HCV treatment, the use of highly active antiretroviral therapy with careful monitoring for hepatotoxicity and aggressive counseling on alcohol and substance abuse may slow down fibrosis progression. As the data on liver transplantation in coinfected patients accumulate, patients with end stage liver disease should be referred early for evaluation in a transplant center. As new drugs for HCV are being developed, it will be of utmost importance to include coinfected patients earlier in the process on new drug trials and therapeutic strategies.


DNA synthesis in the thymus of the adult newt Notophthalmus viridescens.
Lymphocytic activity was examined in thymuses of adult newts by studying the number, location, morphology and fate of cells within thymuses which had been processed for autoradiography 15 min, 2 and 4 h, and 2, 4, and 10 days subsequent to the injection of tritiated thymidine. Results of this study indicate (1) that the adult thymus is a highly proliferative organ, (2) that large and medium-sized lymphocytes present in the peripheral parenchyma give rise to smaller lymphocytes which move centrally and emigrate from the thymus, and (3) that many thymocytes leave the thymus within 2-4 days after they have been produced. The significance of these findings is discussed.


C-Terminal truncation affects subunit exchange of human alphaA-crystallin with alphaB-crystallin.
In human lenses, C-terminal cleavage of alphaA-crystallin at residues 172,168, and 162 have been reported. The effect of C-terminal truncation of alphaA-crystallin on subunit exchange and heterooligomer formation with alphaB-crystallin and homooligomer formation with native alphaA-crystallin is not known. We have conducted fluorescence resonance energy transfer studies which have shown that the rates of subunit exchange of alphaA(1-172 )and alphaA(1-168 )with alphaB-wt were two-fold lower than for alphaA-wt interacting with alphaB-wt. The subunit exchange rate between alphaA(1-162) and alphaB-wt was six-fold lower. These data suggest that cleavage of the C-terminal residues could significantly affect heterooligomerization. On the other hand, the subunit exchange rates between alphaA-wt and the truncated alphaA-crystallins were either unchanged or only slightly decreased, which suggest that homooligomerization may not be significantly influenced by C-terminal truncation. The main conclusion from this study is that cleavage of C-terminal residues of alphaA-crystallin including the nine residues of the flexible tail is expected to significantly affect the formation of heteroaggregates. Reconstitution experiments showed that the presence of an intact C-terminus is essential for the formation of fully integrated heteroaggregates with equal proportion of alphaA and alphaB subunits.


Molecular Mobility and Stability Studies of Amorphous Imatinib Mesylate.
The proposed study examined the characterization and stability of solid-state amorphous imatinib mesylate (IM) after 15 months under controlled relative humidity (60 ± 5%) and temperature (25 ± 2 °C) conditions. After 2 weeks, and 1, 3, 6, and 15 months, the samples were characterized using differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), X-ray powder diffractometry (XRPD), attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) and scanning electron microscopy (SEM). Additionally, the amorphous form of imatinib mesylate was obtained via supercooling of the melt in a DSC apparatus, and aged at various temperatures (3, 15, 25 and 30 °C) and time periods (1-16 h). Glass transition and enthalpy relaxation were used to calculate molecular-relaxation-time parameters. The Kohlrausch-Williams-Watts (KWW) equation was applied to fit the experimental enthalpy-relaxation data. The mean molecular-relaxation-time constant (τ) increased with decreasing ageing temperature. The results showed a high stability of amorphous imatinib mesylate adequate to enable its use in solid dosage form.


A founder EIF2AK4 mutation causes an aggressive form of pulmonary arterial hypertension in Iberian Gypsies.
Pulmonary arterial hypertension (PAH) is a pathological condition characterized by a persistent and progressive elevation of pulmonary vascular resistance with devastating consequences if untreated. In the past recent years, several genes have been related to PAH, however, the molecular defect remains unknown in a significant proportion of patients with familial PAH (∼20%). During the past few years, we have observed that PAH shows a particular behavior in Iberian Gypsies, with more aggressive course and frequently affecting multiple members of the same family. We studied five Gypsy families in whom at least one individual from each family developed a severe form of PAH and in whom no mutation had been identified in the common genes. We applied SNP-array-based homozygosity mapping in three families and obtained, among others, one of which included the gene EIF2AK4, recently reported in patients with PAH from group-1' pulmonary veno-occlusive disease (PVOD) and pulmonary capillary hemangiomatosis (PCH). Subsequently, we sequenced EIF2AK4 and found a homozygous mutation in all five families: c.3344C>T(p.P1115L). The majority of our patients required early lung transplantation. Hence, this mutation appeared with a more severe phenotype than previously reported for other EIF2AK4 mutations. The finding of this novel mutation is important for genetic counseling and calculation of population recurrence risks.


Mirtazapine in schizophrenia - an undeservedly overlooked option?
Mirtazapine has often been prescribed as add-on treatment for schizophrenia in patients with suboptimal response to conventional treatments. In this review, we evaluate the existing evidence for efficacy and effectiveness of add-on mirtazapine in schizophrenia and reappraise the practical and theoretical aspects of mirtazapine-antipsychotic combinations. In randomized controlled trials (RCTs), mirtazapine demonstrated favourable effects on negative and cognitive (although plausibly not depressive) symptoms, with no risk of psychotic exacerbation. Mirtazapine also may have a desirable effect on antipsychotic-induced sexual dysfunction, but seems not to alleviate extrapyramidal symptoms, at least if combined with second-generation antipsychotics. It is noteworthy that all published RCTs have been underpowered and relatively short in duration. In the only large pragmatic effectiveness study that provided analyses by add-on antidepressant, only mirtazapine was associated with both decreased rate of hospital admissions and number of in-patient days. Mirtazapine hardly affects the pharmacokinetics of antipsychotics. However, possible pharmacodynamic interactions (sedation and metabolic offence) should be borne in mind. The observed desired clinical effects of mirtazapine may be due to its specific receptor-blocking properties. Alternative theoretical explanations include its possible neuroprotective effect. Further well-designed RCTs and real-world effectiveness studies are needed to determine whether add-on mirtazapine should be recommended for difficult-to-treat schizophrenia.


Masticatory loading and bone adaptation in the supraorbital torus of developing macaques.
Research on the evolution and adaptive significance of primate craniofacial morphologies has focused on adult, fully developed individuals. Here, we investigate the possible relationship between the local stress environment arising from masticatory loadings and the emergence of the supraorbital torus in the developing face of the crab-eating macaque Macaca fascicularis. By using finite element analysis (FEA), we are able to evaluate the hypothesis that strain energy density (SED) magnitudes are high in subadult individuals with resulting bone growth in the supraorbital torus. We developed three micro-CT-based FEA models of M. fascicularis skulls ranging in dental age from deciduous to permanent dentitions and validated them against published experimental data. Applied masticatory muscle forces were estimated from physiological cross-sectional areas of macaque cadaveric specimens. The models were sequentially constrained at each working side tooth to simulate the variation of the bite point applied during masticatory function. Custom FEA software was used to solve the voxel-based models and SED and principal strains were computed. A physiological superposition SED map throughout the face was created by allocating to each element the maximum SED value from each of the load cases. SED values were found to be low in the supraorbital torus region throughout ontogeny, while they were consistently high in the zygomatic arch and infraorbital region. Thus, if the supraorbital torus arises to resist masticatory loads, it is either already adapted in each of our subadult models so that we do not observe high SED or a lower site-specific bone deposition threshold must apply.


Activation of 5-hydroxytryptamine-1A receptors suppresses cardiovascular responses evoked from the paraventricular nucleus.
Activation of central 5-hydroxytryptamine-1A (5-HT(1A)) receptors powerfully inhibits stress-evoked cardiovascular responses mediated by the dorsomedial hypothalamus (DMH), as well as responses evoked by direct activation of neurons within the DMH. The hypothalamic paraventricular nucleus (PVN) also has a crucial role in cardiovascular regulation and is believed to regulate heart rate and renal sympathetic activity via pathways that are independent of the DMH. In this study, we determined whether cardiovascular responses evoked from the PVN are also modulated by activation of central 5-HT(1A) receptors. In anesthetized rats, the increases in heart rate and renal sympathetic nerve activity evoked by bicuculline injection into the PVN were greatly reduced (by 54% and 61%, respectively) by intravenous administration of (±)-8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), an agonist of 5-HT(1A) receptors, but were then completely restored by subsequent administration of WAY-100635, a selective antagonist of 5-HT(1A) receptors. Microinjection of 8-OH-DPAT directly into the PVN did not significantly affect the responses to bicuculline injection into the PVN, nor did systemic administration of WAY-100635 alone. In control experiments, a large renal sympathoexcitatory response was evoked from both the PVN and DMH but not from the intermediate region in between; thus the evoked responses from the PVN were not due to activation of neurons in the DMH. The results indicate that activation of central 5-HT(1A) receptors located outside the PVN powerfully inhibits the tachycardia and renal sympathoexcitation evoked by stimulation of neurons in the PVN.


A brief overview of single-port laparoscopic appendectomy as an optimal surgical procedure for patients with acute appendicitis: still a long way to go.
Single-port laparoscopic appendectomy (SPLA) has become a good alternative to the traditional surgical treatment of acute appendicitis, due to its advantages of small incision, mild postoperative pain, short hospital stay, and good cosmetic effect. However, the further application of SPLA has been restricted by its relatively long operating time, high level of operating difficulty, and increased equipment and technical requirements. Clinical teams worldwide have attempted to improve and optimize SPLA technical protocols and equipment to maintain stable intraoperative pneumoperitoneal pressure, improve the 'triangle relationship' of operating angles, and develop new surgical procedures with less trauma and higher cost-effectiveness. Here, new SPLA techniques reported over the past decade are reviewed and compared, with the aim of providing new insights into technical improvements, equipment upgrades and clinical studies in the coming years.


Determination of antitrypsin activity on agar plates: relationship between antitrypsin and biological value of soybean for trout.
A new method is described for determination of antitrypsin activity based on inhibition of trypsin solubilization of calcium caseinate in agar plates. The method was applied to analyze soybeans after graded heat treatments for their antitrypsin content. Biological determination of protein and energy values of the soybean samples showed direct correlation of these values with the destruction of antitrypsin as measured by the new method, using rainbow trout.


Anxiety Levels of Primary Caregivers of Children With Tracheostomy During the COVID-19 Pandemic.
We aim to evaluate the anxiety levels of caregivers of children with tracheostomy during the COVID-19 (coronavirus disease 2019) pandemic. Caregivers of 31 children with tracheostomy and 105 healthy children (control group) were included. The State-Trait Anxiety Inventory was administered via teleconference in order to investigate how participants describe how they feel at a particular moment (State) and how they generally feel (Trait). The trait anxiety levels of caregivers of children with tracheostomy were significantly higher (P = .02). Their state anxiety levels were similar. The state and trait anxiety levels of caregivers of children with tracheostomy correlated (r = 0.70, P < .001). At the end of the teleconference, caregivers of children with tracheostomy experienced greater anxiety relief than controls (P < .001). Trait anxiety scores were higher among caregivers of children with tracheostomy, but their state anxiety levels were comparable to those of controls. Caregivers with high trait anxiety also exhibited high state anxiety. Informing caregivers of children with tracheostomy about COVID-19 via teleconference can reduce their anxiety during such stressful times.


An inhibitory effect on the nuclear accumulation of phospho-STAT1 by its unphosphorylated form.
Unphosphorylated signal transducer and activator of transcription 1 (U-STAT1) has been reported to elicit a distinct gene expression profile as compared to tyrosine-phosphorylated STAT1 (P-STAT1) homodimers. However, the impact of U-STAT1 on the IFNγ-induced immune response mediated by P-STAT1 is unknown. By generating a double mutant of STAT1 with mutation R602L in the Src-homology 2 (SH2) domain and Y701F in the carboxy-terminal transactivation domain mimicking U-STAT1, we investigated the effects of U-STAT1 on P-STAT1-mediated signal transduction. In this study, we discovered a novel activity of U-STAT1 that alters the nucleo-cytoplasmic distribution of cytokine-stimulated P-STAT1. While the dimerization-deficient mutant R602L/Y701F was not able to display cytokine-induced nuclear accumulation, it inhibited the nuclear accumulation of co-expressed IFNγ-stimulated wild-type P-STAT1. Disruption of the anti-parallel dimer interface in the R602L/Y701F mutant via additional R274W and T385A mutations did not rescue the impaired nuclear accumulation of co-expressed P-STAT1. The mutant U-STAT1 affected neither the binding of co-expressed P-STAT1 to gamma-activated sites in vitro, nor the transcription of reporter constructs and the activation of STAT1 target genes. However, the nuclear accumulation of P-STAT1 was diminished in the presence of mutant U-STAT1, which was not restored by mutations reducing the DNA affinity of mutant U-STAT1. Whereas single mutations in the amino-terminus of dimerization-deficient U-STAT1 similarly inhibited the nuclear accumulation of co-expressed P-STAT1, a complete deletion of the amino-terminus restored cytokine-stimulated nuclear accumulation of P-STAT1. Likewise, the disruption of a dimer-specific nuclear localization signal also rescued the U-STAT1-mediated inhibition of P-STAT1 nuclear accumulation. Our data demonstrate a novel role of U-STAT1 in affecting nuclear accumulation of P-STAT1, such that a high intracellular concentration of U-STAT1 inhibits the detection of nuclear P-STAT1 in immunofluorescence assays. These observations hint at a possible physiological function of U-STAT1 in buffering the nuclear import of P-STAT1, while preserving IFNγ-induced gene expression. Based on these results, we propose a model of a hypothetical import structure, the assembly of which is impaired under high concentrations of U-STAT1. This mechanism maintains high levels of cytoplasmic STAT1, while simultaneously retaining signal transduction by IFNγ. Video Abstract.


Tailored Precision: A Unique Case of Pelvic Osteosarcoma Management.
Osteosarcoma of the pelvis poses challenges in surgical resection due to its anatomical location and extensive nature. This case report focuses on the clinical presentation and therapeutic outcomes of a 20-year-old patient with osteosarcoma of the right iliac bone. The study highlights the efficacy of 3D printing technology in creating customized implants for improved surgical outcomes. The case report presents the clinical presentation, management, and outcomes of a patient with osteosarcoma of the right iliac bone. It emphasizes the impact of surgical resection extent and endoprosthetic reconstruction. The study highlights the advantages of 3D printing technology in creating customized implants that accurately fit the remaining bone. Limb-sparing surgery is advocated for better functional and psychological outcomes compared to amputation. The report also emphasizes the need for further research on alternative composite materials and discusses the limitations of 3D printing technology in orthopedics.The limitations of 3D printing, such as mechanical safety and material restrictions, are discussed, calling for future advancements to improve the reliability and effectiveness of 3D-printed implants in orthopedics. The present case report provides valuable perspectives into the efficacious management of pelvic osteosarcoma and underscores the distinctive advantages of 3D printing technology in improving surgical results. Limb-sparing surgery demonstrates enhanced functional and psychological outcomes compared to amputation. Utilizing 3D custom-made implants, significantly reduces the likelihood of revision surgeries attributed to implant failure, improves the surgical outcome and precision.


Silver-Catalyzed Trifluoromethylalkynylation of Unactivated Alkenes with Hypervalent Iodine Reagents.
A catalytic method for the trifluoromethylalkynylation of unactivated alkenes is presented. The reaction is catalyzed by silver(I) trifluoroacetate for the simultaneous construction of two C-C bonds (alkyl-alkyne and alkyl-CF3). By employing versatile hypervalent iodine reagents, ethynylbenziodoxolones, useful trifluoromethylalkynylated compounds can be prepared from simple alkenes displaying excellent functional group tolerability. A radical mechanism is proposed with supporting evidence, providing a new entry to silver(I)-catalyzed trifluoromethylation reactions.


Advancing and critical appraisal of an integrative load monitoring approach in microcycles in professional soccer.
Despite load monitoring being considered an integral part of targeted performance management, including injury and illness prevention, there is currently no consensus of an effective monitoring system in professional soccer. Thus, the aims were to apply an integrative load monitoring approach, previously established in rink-hockey, in professional soccer; extend this approach with further data (Short Recovery and Stress Scale); assess this (extended) approach, thereby further evaluating the relationship between the used external load (EL) measures (total distance, distance above 55% and 70% of individual maximal speed, number of accelerations and decelerations > 4 m/s2, total loading) and the internal load (IL) measure session rate of perceived exertion training load (sRPE-TL) as well as between the used EL measures and sRPE. This retrospective observational cohort study analyzed data from a Swiss team collected over a 14 week-period during the 2021/22 season. Based on our findings, the integrative approach tested proved to be an applicable load monitoring tool in professional soccer, placing players on a fitness-fatigue continuum throughout the different microcycle sessions without using tests, thus providing relevant information to individually tailor training programs. sRPE-TL (ρ [95% CI] = .55 [.51 to .59] to .87 [.85 to .88]; all p < .001) better reflected the EL experienced by players than sRPE (ρ [95% CI] = .45 [.40 to .50] to .71 [.69 to .75]; all p < .001) supporting the definition of sRPE-TL as a measure of IL. However, for even stronger relevance of the tested tool, further research is warranted, especially to ascertain its sensitivity and determine an optimal selection of EL and IL measures. In sum, the present data clearly demonstrate the importance of load management taking place at an individual level, even within team structures, thereby analyzing a set of both EL and IL measures.


[Effects of angiotensin-converting enzyme on reproduction of Culex pipiens pallens].
To investigate the role of angiotensin-converting enzyme (ACE) in the reproduction of Culex pipiens pallens, so as to provide insights into selection of targets for controlling mosquito vector populations. Cx. pipiens pallens was collected from Tangkou County, Shandong Province in 2009. Female and male mosquitoes were selected at 72 hours post-eclosion, and quantitative real-time reverse transcription PCR (qPCR) assay was used to detect the expression of ACE gene in the whole body and reproductive tissues of male mosquitoes and fertilized female mosquitoes before (0 h) and after blood meals (24, 48, 72 h), respectively. Then, 150 female and 150 male mosquitoes at 0 to 4 hours post-eclosion were selected and divided into the wild-type group (WT group), small interfering RNA-negative control group (siNC group) and small interfering RNA-ACE group (siACE group), of 50 mosquitoes in each group. Mosquitoes in the WT group were given no treatment, and mosquitoes in the siNC and siACE groups were given microinjection of siNC and siACE into the hemolymph at a dose of 0.3 μg per mosquito. The knockdown efficiency was checked using qPCR assay, and the reproductive phenotype of mosquitoes was observed. The relative ACE gene expression was higher in the whole body of male mosquitoes (5.467 ± 1.006) relative to females (1.199 ± 0.241) (t = 5.835, P = 0.004) at 72 h post-eclosion, and the highest ACE expression was seen in reproductive tissues of male mosquitoes (199.100 ± 24.429), which was 188.3 times higher than in remaining tissues (1.057 ± 0.340) (t = 6.602, P = 0.002). Blood meal induced high ACE expression in all body tissues of fertilized female mosquitoes, with peak expression at 24 h after blood meals (14.957 ± 2.815), which was 14.8 times higher than that before blood meals (1.009 ± 0.139) (P = 0.002). The transcriptional level of ACEs continued to increase in the ovaries of female mosquitoes after blood meals during the vitellogenesis phase, peaking at 48 h after blood meals (5.500 ± 0.734), which was 5.1 times higher than that before blood meals (1.072 ± 0.178) (P = 0.002). Small RNA interference targeting ACE resulted in a 57.2% reduction in ACE expression in female mosquitoes in the siACE group (0.430 ± 0.070) relative to the siNC group (1.002 ± 0.070) (P = 0.001), and a 41.1% reduction in male mosquitoes in the siACE group (0.588 ± 0.067) relative to the siNC group (1.008 ± 0.131) (P = 0.016). Knockdown of ACE expression resulted in a 48.0% decrease in the number of eggs laid by female mosquitoes in the siACE group [(94.000 ± 27.386) eggs] relative to the siNC group [(180.800 ± 27.386)] (P < 0.001), and a 45.0% decrease in the number of eggs laid by wild female mosquitoes mated with males in the siACE group [(104.500 ± 20.965) eggs] relative to the siNC group [(190.050 ± 10.698) eggs] (P < 0.001). Reduced ACE expression may inhibit the fecundity of male and female mosquitoes, and ACE may be as a potential target for mosquito vector population suppression.


Uncertainties in thyroid dose reconstruction after Chernobyl.
The most significant impact of the Chernobyl accident of 26 April 1986 is the increased incidence of thyroid cancer among Belarusians, Russians and Ukrainians who were exposed as children to radioiodines in fallout resulting from atmospheric releases. The US National Cancer Institute (NCI), in cooperation with the ministries of health of Belarus and Ukraine, is involved in epidemiological studies of thyroid diseases related to the accident. Individual thyroid doses, as well as uncertainties, have been estimated for the members of the cohort studies (approximately 13,000 Ukrainians and 12,000 Belarusians). The cohort subjects, who were selected from the large group of children whose thyroids were monitored for gamma radiation within a few weeks of the accident, provided personal information on their residence history and dietary habits during interviews. Thyroid dose estimates range from 1 mGy to more than 20 Gy. The uncertainties are found to be approximately log-normally distributed, with geometric standard deviations ranging from 1.6 to 5.0. The medians of the geometric standard deviations are 1.7 for the Ukrainian subjects and 2.1 for the Belarusian subjects. The major sources of uncertainty in the thyroid dose estimates are found to be those related to the thyroid mass of the subject and to the estimation of the thyroidal content of 131I at the time of thyroid monitoring.


Human ovarian surface epithelial cells immortalized with hTERT maintain functional pRb and p53 expression.
Cell immortalization is considered to be a prerequisite status for carcinogenesis. Normal human ovarian surface epithelial (OSE) cells, which are thought to be the origin of most of human ovarian carcinomas, have a very limited lifespan in culture. Establishment of immortalized OSE cell lines has, in the past, required inactivation of pRb and p53 functions. However, this often leads to increased chromosome instability during prolonged culture. In this study, we have used a retroviral infection method to overexpress human telomerase reverse transcriptase (hTERT) gene, in primary normal OSE cells, under optimized culture conditions. In vitro and in vivo analysis of hTERT-immortalized cell lines confirmed their normal epithelial characteristics. Gene expression profiles and functional analysis of p16(INK4A), p15(INK4B), pRb and p53 confirmed the presence of their intact functions. Our study suggests that inactivation of pRb and p53 is not necessary for OSE immortalization. Furthermore, down-regulation of p15(INK4B) in the immortalized cells may indicate a functional role for this protein in them. These immortal OSE cell lines are likely to be an important tool for studying human OSE biology and carcinogenesis.


Targeting Small GTPases and Their Prenylation in Diabetes Mellitus.
A fundamental role of pancreatic β-cells to maintain proper blood glucose level is controlled by the Ras superfamily of small GTPases that undergo post-translational modifications, including prenylation. This covalent attachment with either a farnesyl or a geranylgeranyl group controls their localization, activity, and protein-protein interactions. Small GTPases are critical in maintaining glucose homeostasis acting in the pancreas and metabolically active tissues such as skeletal muscles, liver, or adipocytes. Hyperglycemia-induced upregulation of small GTPases suggests that inhibition of these pathways deserves to be considered as a potential therapeutic approach in treating T2D. This Perspective presents how inhibition of various points in the mevalonate pathway might affect protein prenylation and functioning of diabetes-affected tissues and contribute to chronic inflammation involved in diabetes mellitus (T2D) development. We also demonstrate the currently available molecular tools to decipher the mechanisms linking the mevalonate pathway's enzymes and GTPases with diabetes.


Non-alcoholic fatty liver disease incidence and remission and their predictors during 7 years follow-up among Finns.
The incidence and remission of non-alcoholic fatty liver disease (NAFLD) are sparsely studied outside Asia. This prospective study aimed to investigate NAFLD incidence and remission, and their predictors among a general Finnish population. The applied cohort included 1260 repeatedly studied middle-aged participants with data on liver ultrasound and no excessive alcohol intake. Hepatic steatosis was assessed by liver ultrasound with 7.2-year study interval. Comprehensive data on health parameters and lifestyle factors were available. At baseline 1079 participants did not have NAFLD, and during the study period 198 of them developed NAFLD. Of the 181 participants with NAFLD at baseline, 40 achieved NAFLD remission. Taking multicollinearity into account, key predictors for incident NAFLD were baseline age (odds ratio 1.07, 95% confidence interval 1.02-1.13, P=0.009), waist circumference (WC) (2.77, 1.91-4.01 per one standard deviation [SD], P<0.001), and triglycerides (2.31, 1.53-3.51 per one SD, P<0.001) and alanine aminotransferase (ALAT) (1.90, 1.20-3.00 per one SD, P=0.006) concentrations as well as body mass index (BMI) change (4.12, 3.02-5.63 per one SD, P<0.001). Predictors of NAFLD remission were baseline aspartate aminotransferase (ASAT) concentration (0.23, 0.08-0.67 per one SD, P=0.007) and WC change (0.38, 0.25-0.59 per one SD, P<0.001). During the follow-up, NAFLD developed for every fifth participant without NAFLD at baseline, and a fifth of those with NAFLD at baseline had achieved NAFLD remission. NAFLD became more prevalent during the follow-up. From a clinical perspective, key factors predicting NAFLD incidence and remission were BMI and WC change independent of their baseline level.


[The development of slit pictures].
The development of the slit-pictures, which goes back to the oldest times of radiology, is going to be discussed. Todays methods are reviewed. In the beginning only used for the elimination of the secondary radiation and for the orthograde pictures, the author has proposed many years ago to use the slit-pictures-technic and represented by model-experiments for change the X-ray perspective, which by shifting the both slit-diaphragmas, the X-ray-tube, the patient and the film different pictures effects are gained. So the direction of radiation changes during the exposition. In the next time some of these methods were practised, e.g. the "Panoramaaufnahme" of the skull and the jaws, the total picture of the vertebral columne, the arteriography of the limbs and so on. As a new technic are the "Einblicksaufnahme" of the vertebral canal and the picture of the Os ethmoidale, which is unfolded like the pages of a open book, also the picture of a conio-section of an object. The mathematical analysis of the slit-pictures by Vuoria (Vuorinen) is discussed, further the examination of quality and the radiation load. Finally application of digital technics on slit-pictures is proposed and this combination is discussed.


Cerebrovascular responses to carbon dioxide as detected by near-infrared spectrophotometry: comparison of three different measures.
Near-infrared spectrophotometry can be used to measure cerebral concentrations of oxyhemoglobin and deoxyhemoglobin. This has been applied to developing methods for quantifying cerebral blood volume (CBV), which is relevant for the investigation of the pathogenesis of brain injury in newborn infants as well as older infants. This study investigates the internal consistency between measurements of CBV using two methods: the oxygen method, which is able to determine absolute values of CBV, and the total Hb method, which can detect changes in CBV only. Cerebral blood flow (CBF) was also measured. Fifteen premature infants were examined. Due to practical problems, in only eight of these was a minimum of two CBF and two CBV values obtained both before and after a change in arterial PCO2 of at least 0.5 kPa. A significant difference between the CBV-CO2 reactivity found by the two methods was demonstrated: 0.89 mL/100 g/kPa (95% confidence interval = 0.63-1.26) for the oxygen method and 0.22 mL/100 g/kPa (95% confidence interval = 0.08-0.36) for the total Hb method. This finding is substantiated by the absolute values of CBV [mean value = 3.7 mL/100 g (SD = 1.1)], CBF [mean value = 11.3 mL/100 g/min (SD = 5.9)], and CBF reactivity [59 +/- 9% (SEM)]. All the values correspond well with previous findings, although the CBV reactivity determined by the oxygen method has not been reported previously. The reason for the discrepancy between the two methods is unclear, but induced changes in the scattering properties of the brain would give rise to errors influencing the total Hb method rather than the oxygen method.


Medical gases for stroke therapy: summary of progress 2015-2016.
Stroke is a cerebrovascular disease with high mortality and morbidity. Despite extensive research, there are only a very limited number of therapeutic approaches suitable for treatment of stroke patients as yet. Mounting evidence has demonstrated that such gases as oxygen, hydrogen and hydrogen sulfide are able to provide neuroprotection after stroke. In this paper, we will focus on the recent two years' progress in the development of gas therapies of stroke and in understanding the molecular mechanisms underlying protection induced by medical gases. We will also discuss the advantages and challenges of these approaches and provide information for future study.


[Reaction of bovine endothelial cells in vitro to coccidia (Eimeria bovis, Toxoplasma gondii, Neospora caninum) infections as the expression of a non-adaptive immune response].
Eimeria (E.) bovis sporozoites as well as Toxoplasma (T.) gondii and Neospora (N.) caninum tachyzoites can invade bovine endothelial cells (BUVEC) in vitro and develop to next stage meronts within 15-20 and 3-4 days, respectively. The latter differences suggest different immune evasion strategies, particularly concerning innate reactions. Realtime RT-PCR techniques were used to determine transcript levels of genes relevant in this sense, i.e. adhesion molecule, chemokine, growth factor GM-CSF, cyclooxygenase 2 (COX-2) and iNOS genes in infected cells. In addition, adhesion of neutrophils (PMN) to infected BUVEC monolayers was quantified. Effects differed between E. bovis and T. gondii/N. caninum as the latter two species strongly enhance the transcription of all genes in question and induce PMN adhesion to infected BUVEC whereas E. bovis either caused only weak responses or failed to enhance gene transcription as in case of CXC chemokines and COX-2. It even down regulates adhesion molecule expression in response to cytokines. The differences between the species may reflect differing immune evasion strategies, in case of E. bovis favouring its long lasting development to macromeronts.


Systemic thioridazine in combination with dicloxacillin against early aortic graft infections caused by Staphylococcus aureus in a porcine model: In vivo results do not reproduce the in vitro synergistic activity.
Conservative treatment solutions against aortic prosthetic vascular graft infection (APVGI) for inoperable patients are limited. The combination of antibiotics with antibacterial helper compounds, such as the neuroleptic drug thioridazine (TDZ), should be explored. To investigate the efficacy of conservative systemic treatment with dicloxacillin (DCX) in combination with TDZ (DCX+TDZ), compared to DCX alone, against early APVGI caused by methicillin-sensitive Staphylococcus aureus (MSSA) in a porcine model. The synergism of DCX+TDZ against MSSA was initially assessed in vitro by viability assay. Thereafter, thirty-two pigs had polyester grafts implanted in the infrarenal aorta, followed by inoculation with 106 CFU of MSSA, and were randomly administered oral systemic treatment with either 1) DCX or 2) DCX+TDZ. Treatment was initiated one week postoperatively and continued for a further 21 days. Weight, temperature, and blood samples were collected at predefined intervals. By termination, bacterial quantities from the graft surface, graft material, and perigraft tissue were obtained. Despite in vitro synergism, the porcine experiment revealed no statistical differences for bacteriological endpoints between the two treatment groups, and none of the treatments eradicated the APVGI. Accordingly, the mixed model analyses of weight, temperature, and blood samples revealed no statistical differences. Conservative systemic treatment with DCX+TDZ did not reproduce in vitro results against APVGI caused by MSSA in this porcine model. However, unexpected severe adverse effects related to the planned dose of TDZ required a considerable reduction to the administered dose of TDZ, which may have compromised the results.


Cardiovascular effects of ephedrine, caffeine and yohimbine measured by thoracic electrical bioimpedance in obese women.
Low caloric diet is a commonly accepted treatment in obesity. However, owing to moderate results, a pharmacological support has been proposed. As some efficacious drugs activate overall sympathetic activity, they might modify functions of the cardiovascular system. Three groups of subjects were studied: (1) nine obese women receiving only a standard hypocaloric diet; (2) nine obese women receiving a standard hypocaloric diet and ephedrine (2 x 25 mg) with caffeine (2 x 200 mg); (3) nine obese women receiving a standard hypocaloric diet and ephedrine (2 x 25 mg) with caffeine (2 x 200 mg) and yohimbine (2 x 5 mg). The cardiovascular state was evaluated by thoracic electrical bioimpedance, automatic sphygmomanometry and continuous ECG recording. In each patient, the haemodynamic study was performed twice: at rest, i.e. before treatment; and after 10 days of treatment. On the same days in each patient, the haemodynamic tests were performed during physical exercises (handgrip stress and cycloergometer exercise). Caffeine and ephedrine had no haemodynamic effect in resting patients. These two drugs led to an increase in ejection fraction during cycloergometer exercise. Addition of yohimbine increased diastolic pressure and heart rate but decreased ejection fraction and stroke index during rest. We also observed that addition of yohimbine decreased ejection fraction during the handgrip and cycloergometer exercise and increased cardiac load during dynamic exercise. Pharmacological supplement of ephedrine and caffeine to a low caloric diet modified the cardiovascular system weakly, but the addition of yohimbine to this regimen attenuated cardiac performance during rest and handgrip and increased cardiac work during dynamic exercise.


Pneumocystis Pneumonia Concomitant with Ectopic ACTH Syndrome Caused by a Large Cell Neuroendocrine Carcinoma of the Thymus.
We herein report the case of a 44-year-old man who was diagnosed with pneumocystis pneumonia (PCP) concomitant with ectopic adrenocorticotropic hormone (ACTH) syndrome, which had been caused by a large cell neuroendocrine carcinoma of the thymus. Chest computed tomography revealed ground-glass opacities in the lungs. PCP was diagnosed by a polymerase chain reaction with bronchoalveolar lavage. The levels of cortisol were slowly corrected with an adrenal enzyme inhibitor, and the exacerbation of PCP was successfully avoided. Our case indicates that in addition to prophylaxis, the early diagnosis of PCP and the slow correction of hypercortisolemia should be considered in order to prevent an exacerbation due to the reconstitution of the immune function in patients with ectopic ACTH syndrome.


Synergistic combinations of multiple chemotherapeutic agents in high capacity poly(2-oxazoline) micelles.
Many effective drugs for cancer treatment are poorly water-soluble. In combination chemotherapy, needed excipients in additive formulations are often toxic and restrict their applications in clinical intervention. Here, we report on amphiphilic poly(2-oxazoline)s (POx) micelles as a promising high capacity delivery platform for multidrug cancer chemotherapy. A variety of binary and ternary drugs combinations of paclitaxel (PTX), docetaxel (DTX), 17-allylamino-17-demethoxygeldanamycin (17-AAG), etoposide (ETO) and bortezomib (BTZ) were solubilized in defined polymeric micelles achieving unprecedented high total loading capacities of up to 50 wt % drug per final formulation. Multidrug loaded POx micelles showed enhanced stability in comparison to single-drug loaded micelles. Drug ratio dependent synergistic cytotoxicity of micellar ETO/17-AAG was observed in MCF-7 cancer cells and of micellar BTZ/17-AAG in MCF-7, PC3, MDA-MB-231 and HepG2 cells.


Multi-scale characterization of symbiont diversity in the pea aphid complex through metagenomic approaches.
Most metazoans are involved in durable relationships with microbes which can take several forms, from mutualism to parasitism. The advances of NGS technologies and bioinformatics tools have opened opportunities to shed light on the diversity of microbial communities and to give some insights into the functions they perform in a broad array of hosts. The pea aphid is a model system for the study of insect-bacteria symbiosis. It is organized in a complex of biotypes, each adapted to specific host plants. It harbors both an obligatory symbiont supplying key nutrients and several facultative symbionts bringing additional functions to the host, such as protection against biotic and abiotic stresses. However, little is known on how the symbiont genomic diversity is structured at different scales: across host biotypes, among individuals of the same biotype, or within individual aphids, which limits our understanding on how these multi-partner symbioses evolve and interact. We present a framework well adapted to the study of genomic diversity and evolutionary dynamics of the pea aphid holobiont from metagenomic read sets, based on mapping to reference genomes and whole genome variant calling. Our results revealed that the pea aphid microbiota is dominated by a few heritable bacterial symbionts reported in earlier works, with no discovery of new microbial associates. However, we detected a large and heterogeneous genotypic diversity associated with the different symbionts of the pea aphid. Partitioning analysis showed that this fine resolution diversity is distributed across the three considered scales. Phylogenetic analyses highlighted frequent horizontal transfers of facultative symbionts between host lineages, indicative of flexible associations between the pea aphid and its microbiota. However, the evolutionary dynamics of symbiotic associations strongly varied depending on the symbiont, reflecting different histories and possible constraints. In addition, at the intra-host scale, we showed that different symbiont strains may coexist inside the same aphid host. We present a methodological framework for the detailed analysis of NGS data from microbial communities of moderate complexity and gave major insights into the extent of diversity in pea aphid-symbiont associations and the range of evolutionary trajectories they could take.


Gestational risk factors for Wilms' tumor: results of a case-control study.
Gestational risk factors for Wilms' tumor were investigated in a pair-matched case-control study. Cases who were under 15 years of age at diagnosis during 1970-1983 were identified through the registries of the three main hospitals treating childhood cancer in the greater Philadelphia area. Controls were selected by random digit dialing and were matched to cases on race, birth date, and telephone area code and exchange. Because of a low participation rate among nonwhites, results are reported only for the 88 white matched pairs whose parents were interviewed by telephone. Of the hypothesized risk factors, maternal use of hair-coloring products in the year prior to the index child's birth (odds ratio, 3.6; P = 0.003) and hypertension or fluid retention during pregnancy (odds ratio, 5.0, P = 0.01) were significantly associated with increased risk of Wilms' tumor. Use of hair-coloring products was strongly associated with cases in which Wilms' tumor was diagnosed before 2 years of age (odds ratio, 15; P = 0.001). For two other gestational factors, tea drinking and vaginal infection, the odds ratios were significantly elevated for all cases and the effects were concentrated among the nongenetic cases. Bilateral cases had a significantly higher mean birth weight than did their controls. Older maternal age was significantly associated with the genetic form of Wilms' tumor. Adjustment for possible confounders and consideration of the time interval between the index pregnancy and the interview did not substantially alter the findings.


Metastatic olfactory neuroblastoma invading a radiation-induced meningioma.
Olfactory neuroblastomas are malignant, neuroectodermal nasal tumours. We describe a 62-year-old patient with a recurrent olfactory neuroblastoma invading a radiation-induced meningioma. Given the temporal and spatial relationship between the primary lesion and the described recurrence, this was due to metastatic rather than direct contiguous spread, fulfilling all the criteria for true tumour-to-tumour metastasis. To our knowledge, this is the first description of an olfactory neuroblastoma metastasising to a meningioma.


Complete Genome Sequence of Enterobacter cloacae B2-DHA, a Chromium-Resistant Bacterium.
Previously, we reported a chromium-resistant bacterium, Enterobacter cloacae B2-DHA, isolated from the landfills of tannery industries in Bangladesh. Here, we investigated its genetic composition using massively parallel sequencing and comparative analysis with other known Enterobacter genomes. Assembly of the sequencing reads revealed a genome of ~4.21 Mb in size.


Estimating the intrinsic limit of the Feller-Peterson-Dixon composite approach when applied to adiabatic ionization potentials in atoms and small molecules.
Benchmark adiabatic ionization potentials were obtained with the Feller-Peterson-Dixon (FPD) theoretical method for a collection of 48 atoms and small molecules. In previous studies, the FPD method demonstrated an ability to predict atomization energies (heats of formation) and electron affinities well within a 95% confidence level of ±1 kcal/mol. Large 1-particle expansions involving correlation consistent basis sets (up to aug-cc-pV8Z in many cases and aug-cc-pV9Z for some atoms) were chosen for the valence CCSD(T) starting point calculations. Despite their cost, these large basis sets were chosen in order to help minimize the residual basis set truncation error and reduce dependence on approximate basis set limit extrapolation formulas. The complementary n-particle expansion included higher order CCSDT, CCSDTQ, or CCSDTQ5 (coupled cluster theory with iterative triple, quadruple, and quintuple excitations) corrections. For all of the chemical systems examined here, it was also possible to either perform explicit full configuration interaction (CI) calculations or to otherwise estimate the full CI limit. Additionally, corrections associated with core/valence correlation, scalar relativity, anharmonic zero point vibrational energies, non-adiabatic effects, and other minor factors were considered. The root mean square deviation with respect to experiment for the ionization potentials was 0.21 kcal/mol (0.009 eV). The corresponding level of agreement for molecular enthalpies of formation was 0.37 kcal/mol and for electron affinities 0.20 kcal/mol. Similar good agreement with experiment was found in the case of molecular structures and harmonic frequencies. Overall, the combination of energetic, structural, and vibrational data (655 comparisons) reflects the consistent ability of the FPD method to achieve close agreement with experiment for small molecules using the level of theory applied in this study.


Cascaded two-photon spectroscopy of Yb atoms with a transportable effusive atomic beam apparatus.
We present a transportable effusive atomic beam apparatus for cascaded two-photon spectroscopy of the dipole-forbidden transition (6s(2)(1)S0↔ 6s7s (1)S0) of Yb atoms. An ohmic-heating effusive oven is designed to have a reservoir volume of 1.6 cm(3) and a high degree of atomic beam collimation angle of 30 mrad. The new atomic beam apparatus allows us to detect the spontaneously cascaded two-photons from the 6s7s(1)S0 state via the intercombination 6s6p(3)P1 state with a high signal-to-noise ratio even at the temperature of 340 °C. This is made possible in our apparatus because of the enhanced atomic beam flux and superior detection solid angle.


Impact of physical activity on ovarian reserve markers in normal, overweight and obese reproductive age women.
Physical inactivity is a leading risk factor for overweight and obesity in the society. Prevalence of overweight and obesity in the reproductive age group women not only affects maternal health but also the health of the off spring. Infertility is a common problem in India affecting 13-19 million people at any given time. Even though it is not life threatening, infertility causes intense mental agony and trauma that can only be best described by infertile couples themselves. Infertility is more common in overweight and obese individuals compared to normal weight individuals. Decreasing ovarian reserve is an important factor for infertility in women. This study examined the impact of physical activity on ovarian reserve markers in normal, overweight and obese reproductive age women. The observations made in this study reveal that physical activity improves ovarian reserve markers in all reproductive age women but this improvement is more distinct and statistically significant in overweight and obese women compared to normal weight women.


Awareness of food nutritive value and eating practices among Nigerian bank workers: Implications for nutritional counseling and education.
Adequate nutrition is an important aspect of a healthy lifestyle for all individuals, including bank staff. The objective of this study was to investigate the awareness of food nutritive value and eating practices among bank workers in Lagos State, Nigeria.The study adopted a cross-sectional descriptive survey design. A purposive sample of 250 bank workers took part in the study. Means and Student t tests were employed for data analysis.Results showed that bank workers were aware of the nutritive value of foods, and that eating practices commonly adopted included skipping breakfast, eating breakfast at work, buying food at work from the bank canteen, eating in between meals, buying snacks as lunch, and consuming soft drinks daily, among others. There were no significant differences between male and female bank workers in mean responses on food nutritive value or in eating practices adopted.Good eating habits will help bank workers not only to improve their nutritional well-being, but also to prevent nutrition-related diseases. The implications for nutritional counseling and education are discussed in the context of these findings.


Insulin inhibits Na+/H+ exchange in vascular smooth muscle and endothelial cells in situ: involvement of H2O2 and tyrosine phosphatase SHP-2.
Insulin signals through several intracellular pathways. Here, we tested the hypothesis that insulin modulates Na+/H+ exchange (NHE) activity in vascular cells through H2O2-mediated inhibition of tyrosine phosphatase Src homology 2 domain containing tyrosine phosphatase 2 (SHP-2). We measured intracellular pH (pHi) in isolated mouse mesenteric arteries using fluorescence confocal and wide-field microscopy. In the absence of CO(2)/HCO(3)(-), removal of bath Na(+) produced endothelial acidification (DeltapHi = -0.71 +/- 0.12) inhibited by cariporide. Cariporide reduced endothelial steady-state pHi (DeltapHi=-0.28 +/- 0.08). Insulin and H2O2 acidified endothelial cells 0.2-0.3 pH units and reduced the acidification upon Na+ removal by approximately 65%. Cariporide abolished the effect of insulin and H2O2. In vascular smooth muscle cells, H2O2 produced intracellular acidification (DeltapHi = -0.48 +/- 0.06) as did high concentrations of insulin (DeltapHi = -0.03 +/- 0.01). NHE activity after an NH4+ prepulse was approximately 80% attenuated by H2O2 and approximately 40% by high insulin concentrations. H2O2 had no effect on Na+-HCO3- cotransport activity. NHE1 (slc9a1) was the only plasma membrane NHE isoform detected in mouse mesenteric arteries by RT-PCR analyses. In both cell types, polyethylene glycol catalase abolished the effect of insulin on pHi. Exposure to insulin increased the intracellular concentration of reactive oxygen species estimated with the fluorophore 5-(6)-chloromethyl-2',7'-dichlorodihydrofluorescein. The SHP-2 selective inhibitor NSC-87877 and protein tyrosine phosphatase (PTP) inhibitor IV reduced steady-state pHi up to 0.3 pH units and inhibited NHE activity 60-80%; when applied in combination with insulin or H2O2, no further effect was obtained. We conclude that NHE contributes to pHi regulation in arterial endothelial and smooth muscle cells in situ and is inhibited by insulin and H2O2. We propose that insulin signaling involves H2O2 and inhibition of PTP SHP-2.


Polarization-resolved ultrafast dynamics of the complex polarizability in single gold nanoparticles.
Using a phase-sensitive degenerate four-wave mixing technique in heterodyne detection we measured the ultrafast changes of the complex polarizability in single gold nanoparticles at the surface plasmon resonance. Two components in the nanoparticle nonlinear response are distinguished, depending on the linear polarization direction of pump and probe pulses and particle geometry. One component is quantitatively modeled as the variation of the complex dielectric constant induced by the initial increase in the electron gas temperature following the absorption of the pump pulse, and the subsequent electron thermalization with the lattice and the surrounding. The dependence of the measured four-wave mixing on the probe field polarization direction is well reproduced by including a deviation from spherical symmetry in the nanoparticle dielectric constant. The second component manifests as a significant increase in the measured nonlinearity when the probe field is co-polarized with the pump field at pump-probe time overlap. We attribute this component to the nonlinear response from coherent surface plasmons before dephasing into single electron excitations.


In vivo construction of transgenes in Drosophila.
Transgenic flies are generated by transposon-mediated transformation. A drawback of this approach is the size limit of transposable elements. Here, we propose a novel method that allows the extension of transgenes in vivo. This method is based on an incomplete transgene that has been constructed in vitro and integrated into the Drosophila genome by conventional transgenesis. The incomplete transgene contains two short stretches of DNA homologous to the 5'- and 3'-ends of a larger DNA segment of interest. Between the short stretches of homology an I-SceI recognition site is located. Once activated, I-SceI endonuclease introduces a DNA double-strand break, which triggers ectopic recombination between the stretches of homology and the endogenous locus. Through gap repair, the transgene obtains the complete region of interest in vivo. Our results show that this method is effective for copying up to 28 kb of genomic DNA into the transgene, thereby eliminating the technical difficulties associated with the in vitro construction of large transgenes and extending the size limits of current transgenesis protocols. In general, this method may be a useful technique for genetic engineering of eukaryotic model organisms.


[Effects of cadmium on rice seed germination].
With 319 rice varieties as test objects, this paper studied the effects of cadmium on their seed germination. The results showed that after treated with 10 mg x L(-1) of Cd2+, seed germination rate was less affected, but root growth was restrained evidently. Cadmium had more serious impact on root than on sprout. Different rice varieties had different germination responses to Cd2+, with the sequence of conventional rice (Japonica rice) > hybrid rice (Indianica rice) > conventional rice (Indianica rice). The root length and number of two-line sterilities were restrained more strongly than those of three-line sterilities. Based on their responses to Cd2+, the test 319 varieties were clustered into 3 types, i.e., endurant type, medium type, and sensitive type.


FITNESS CONSEQUENCES OF MULTIPLE PATERNITY IN WILD RADISH, RAPHANUS SATIVUS.
In natural populations, wild radish plants typically mate with 6-8 pollen donors, and seeds of individual fruits are usually sired by 1-4 fathers. Since radish fruits are indehiscent and gravity-dispersed, progeny are most likely to compete with a mixture of full and half siblings. The fitness consequences of single and multiple paternity were investigated in a greenhouse experiment. Seeds of every possible cross in a 5 times 5 reciprocal diallel mating design were assigned to one of three competition regimes (four full siblings, four maternal half siblings, or four unrelated individuals per pot) or were grown as singletons. After 14 weeks, the aboveground biomass of all plants was harvested and oven-dried. The dry weight of singletons was more than three times that of progeny grown in competition, indicating that intraspecific competition had occurred. Full- and half-sib progenies did not differ in mean dry weight. Thus, there was no evidence that multiple paternity enhances this aspect of maternal fitness. However, the competition regime dramatically affected the coefficient of variation in dry weight of progeny within a pot. Weight hierarchies were much more pronounced in pots of half sibs and unrelated neighbors than in pots of full sibs. Also variance in dry weight attributable to sire was greatest in the half-sib and "unrelated neighbors" competition regimes. These results suggest that weight hierarchies reinforce genetic differences among the offspring.


Late presentation of glycogen storage disease types Ia and III in children with short stature and hepatomegaly.
Glycogen storage diseases (GSDs) are a collection of disorders related to glycogen synthesis or degradation that classically present in infancy with hypoglycemia, failure to thrive and hepatomegaly; however, their phenotype can vary significantly. We present the cases of two children, 5 years old and 3.5 years old, who were referred to endocrinology for short stature. They were ultimately found to have hepatomegaly, fasting hypoglycemia, mild elevation of transaminases and ketosis. Laboratory and genetic studies were consistent with double heterozygosity for GSDs Ia and III, with one novel mutation discovered in each patient. Nightly, both children were treated with cornstarch, which resulted in resolution of laboratory abnormalities and improvement in their growth velocity. These cases are unusual in that GSD was diagnosed relatively late in life in patients with no previous history of severe hypoglycemia. They highlight the importance of considering glycogen storage disease in a child presenting with short stature, as it is a treatable disease that can be diagnosed non-invasively with genetic testing.


A guide to requesting outpatient and emergency radiographs.
Radiology is an important adjunct to clinical practice, but for many clinicians, requesting X-rays was something that was learnt on the job. This article provides guidelines on when and how to request X-rays for acute conditions such as head and cervical spine trauma, suspected rib and extremity fractures, low back pain and acute abdominal pain. We also highlight what to write in the request form, in order to obtain maximum value from the examination and allow the radiologist to generate a useful, accurate report.


Cloning of a cDNA encoding the Saussurea medusa chalcone isomerase and its expression in transgenic tobacco.
Chalcone isomerase (CHI; EC 18.104.22.168) is a key enzyme in the flavonoid biosynthesis pathway. We isolated a CHI gene (SmCHI) from a cDNA library derived from Saussurea medusa (Asteraceae) cell cultures. The cDNA and genomic sequences of SmCHI are the same; in other words, this gene is intronless. The coding region of the gene is 699 bp long, and its deduced protein consists of 232 amino acids with a predicted molecular mass of 24 kDa and a pI of 4.7. The deduced amino acid sequence of SmCHI shares 79.3% identity with CHI from Callistephus chinensis, a familial relative to S. medusa; this homology is higher than those with CHI's from any other plant species. A functional bioassay for SmCHI was performed by transforming Nicotiana tabacum plants in the sense or antisense orientation under the regulation of the cauliflower mosaic virus (CaMV) 35S promoter. Transgenic tobacco plants overexpressing sense SmCHI produced up to fivefold total flavonoids over wild-type tobacco plants, mainly due to an enhanced accumulation of rutin. Transgenic tobacco plants with antisense SmCHI accumulated smaller amounts of flavonoids; this is apparently brought about by suppressed expression of the endogenous CHI gene. CHI activities also positively correlated with the amounts of total flavonoids accumulated in the transgenic plants. It is concluded that overexpression of SmCHI can be used as a useful approach to increase flavonoid production in transgenic plants.


Serological evidence of morbillivirus infection in small cetaceans from the Southeast Pacific.
The presence of morbillivirus-specific serum antibodies was examined by an indirect enzyme linked immunosorbent assay (iELISA) and virus neutralization tests in serum samples from 30 dusky dolphins (Lagenorhynchus obscurus), 8 long-snouted common dolphins (Delphinus capensis), 2 inshore and 6 offshore bottlenose dolphins (Tursiops truncatus) and 20 Burmeister's porpoises (Phocoena spinipinnis) taken in fisheries off central Peru in 1993-1995. The sera from six dusky dolphins, one common dolphin and three offshore bottlenose dolphins were positive on a coat of dolphin morbillivirus (DMV) antigen in the iELISA. Several of these sera were also positive when tested against peste des petits ruminants and rinderpest virus antigen. Porpoise morbillivirus and/or DMV neutralizing antibodies were detected in the sera of two bottlenose and three dusky dolphins that reacted positively with DMV antigen in iELISA and also in the sera of one common, one dusky and one bottlenose dolphin that were negative in the iELISA. These results strongly suggest that viruses closely related, or identical, to the cetacean morbillivirus present in the North Atlantic and the Mediterranean Sea infect several species of Delphinidae of the Southeastern Pacific. No convincing morbillivirus-specific antibody positive reactions were detected in the sera from either the Burmeister's porpoises or the inshore bottlenose dolphins.


Effect of the Children and Young People's Health Partnership model of paediatric integrated care on health service use and child health outcomes: a pragmatic two-arm cluster randomised controlled trial.
Paediatric health systems across high-income countries are facing avoidable adverse outcomes and increasing demands and costs. The aim of this study was to compare the effect of an enhanced usual care model with that of an integrated health-care model that offers local health clinics for general paediatric problems and early intervention and care for children and young people with tracer conditions. In this pragmatic two-arm cluster randomised controlled trial, we compared the Children and Young People's Health Partnership (CYPHP) model of care versus enhanced usual care (EUC) among children registered at general practices in south London, UK. The CYPHP trial intervention was delivered between April 1, 2018, and June 30, 2021, and children younger than 16 years during the intervention period and registered at study practices on June 30, 2021, were included in the analysis. A restricted randomisation (1:1) following a computer-generated sequence was done by a masked independent statistician at the level of general practice cluster, stratified by borough (Lambeth or Southwark). Cluster allocation and data collection were masked, with unmasking of trial statisticians before analysis. The CYPHP model comprised all elements of EUC (electronic decision support, a primary care hotline, health checks, self-management support and health promotion, and resilience building and mental health first aid) plus local child health clinics delivered by paediatricians and general practitioners, and a nurse-led early intervention service for children with tracer conditions (asthma, eczema, and constipation). Primary outcomes were non-elective admissions (NELA; admissions coded as an emergency) among the whole trial population up to June 30, 2021, and paediatric quality of life (Pediatric Quality of Life Inventory [PedsQL]) among participants with tracer conditions at 6 months after recruitment. Secondary outcomes were primary and secondary care use, child mental health, parental wellbeing, standardised symptom scores for asthma, eczema, and constipation, health-care quality, and child absences from school and parent absences from work. The trial was registered on ClinicalTrials.gov, NCT03461848, and is complete. The trial was conducted between April 1, 2018, and Dec 31, 2021. In total, 23 general practice clusters, consisting of 70 practices with 97 970 registered children, were randomised to CYPHP (n=11) or EUC (n=12). We found no effect, at the population level, of CYPHP versus EUC on non-elective admissions during the intervention period (adjusted mean incidence rate ratio [IRR] 1·00 [95% CI 0·91 to 1·10], p=0·99). Among children with tracer conditions, we found no difference in paediatric quality of life (PedsQL score) at 6 months (adjusted mean difference -0·033 [95% CI -0·122 to 0·055], p=0·46). As a secondary outcome, among children with tracer conditions and requiring care, NELA rates at 12 months did not differ between the CYPHP and EUC groups (66·1 per 1000 person-years vs 75·3 per 1000 person-years; adjusted mean IRR 0·87 [0·61-1·22], p=0·42). In children requiring care, a statistically significant improvement was observed in eczema symptoms at 6 months from baseline in the CYPHP group versus the EUC group (adjusted mean difference -1·370 [-2·630 to -0·122], p=0·032). Quality of asthma care significantly improved among children in the CYPHP group compared with children in the EUC group. No significant improvement was seen for all other secondary outcomes. Although the CYPHP trial found a null effect for the primary outcomes, we found clinically important improvements in some secondary outcomes including care quality. Previous research has shown that large-scale system change requires time to observe a potential positive effect. Guy's and St Thomas Charity, the Lambeth and Southwark Clinical Commissioning Groups, and Evelina London Children's Hospital.


Coronary Intramural Hematoma Presenting as Acute Coronary Syndrome.
We herein report a case of intramural hematoma without ongoing myocardial ischemia that healed spontaneously with conservative treatment. A 37-year-old woman was admitted due to chest pain. Acute coronary syndrome was diagnosed by electrocardiography and echocardiography. Coronary angiography showed 90% stenosis in the distal portion of the left anterior descending coronary artery, where intravascular ultrasound showed a hematoma, but optical coherence tomography could not detect the entry point. Therefore, we identified the intramural hematoma as the etiology. Because the coronary flow was maintained and chest pain disappeared, we chose conservative treatment. Fifteen days after admission, coronary computed tomography showed an improvement in the intramural hematoma.


[Dry jelly concentrate with vitamins and dietary fiber in patients with IBS with constipation: a comparative controlled study].
Irritable bowel syndrome (IBS) is highly prevalent functional gastrointestinal disorder associated with decrease in quality of life and a high social cost. Diet is one of several therapeutic options in IBS treatment; therefore the development and clinical evaluation of innovative functional food for IBS patients is useful. Dry jelly concentrate containing 3 g inulin, 10 mg curcumin and 1.8 mg of pyridoxine was developed and clinically evaluated. Fifty patients fulfilling the Rome III criteria for IBS-C were randomly assigned into two groups: one received standard diet plus two jelly drinks a day for 2 weeks and control group received standard diet. Response to therapy was recorded on a daily basis using Likert scale of abdominal pain, bloating and feeling of incomplete bowel emptying, frequency of bowel movement, Bristol stool scale, and quality of life assessed by IBSQoL questionnaire before and after the treatment. Intake of functional food product (jelly) containing inulin and curcumin is associated with a significant positive effect on the stool parameters (from 0.6±0.24 to 1.15±0.65 t/d in stool frequency, p=0.001, from 2.62±1.23 to 3.99±1.27, index Bristol scale, p=0.001), a reduce of the severity of abdominal pain (from 1.69±0.71 to 1.36±0.44 Likert scale points, p=0.001), bloating (from 2.03±0.89 to 1.55±0.81 points of Likert scale, p=0.02) and a sense of incomplete bowel emptying (from 2.25±0.98 to 1.68±0.92 points of Likert scale, p=0.001), as well as an increase in quality of life (from 64.5±13.5 to 81.2±9.1%, р=0.05). Patients in control group have improvement in abdominal pain (from 2.16±0.58 to 1.8±0.61 Likert scale points, p=0.05) and bloating (from 2.42±0.83 to 2.16±0.71 Likert scale points, p=0.05) only. During the treatment period no significant adverse events were found. These results indicate that jelly concentrate containing inulin, curcumin and pyridoxine improves abdominal pain score, Bristol scale index and quality of life in patients with IBS-C.


Isolation and characterization of sequences from mouse chromosomal DNA with ARS function in yeasts.
Fragments of chromosomal DNA from a variety of eucaryotes can act as ARSs (autonomously replicating sequence) in yeasts. ARSs enable plasmids to be maintained in extrachromosomal form, presumably because they function as initiation sites for DNA replication. We isolated eight different sequences from mouse chromosomal DNA which function as ARSs in Saccharomyces cerevisiae (bakers' yeast). Although the replication efficiency of the different mouse ARSs in yeasts appears to vary widely, about one-half of them functions as well as the yeast chromosomal sequence ARS1. Moreover, five of the ARSs also promote self replication of plasmids in Schizosaccharomyces pombe (fission yeast). Each of the ARSs was cloned into plasmids suitable for transformation of mouse tissue culture cells. Plasmids were introduced into thymidine kinase (TK)-deficient mouse L cells by the calcium phosphate precipitation technique in the absence of carrier DNA. In some experiments, the ARS plasmid contained the herpes simplex virus type 1 TK gene; in other experiments (cotransformations), the TK gene was carried on a separate plasmid used in the same transformation. In contrast to their behavior in yeasts, none of the ARS plasmids displayed a significant increase in transformation frequency in mouse cells compared with control plasmids. Moreover, only 1 of over 100 cell lines contained the original plasmid in extrachromosomal form. The majority of cell lines produced by transformation with an ARS TK plasmid contained multiple copies of plasmid integrated into chromosomal DNA. In most cases, results with plasmids used in cotransformations were similar to those for plasmids carrying TK. However, cell lines produced by cotransformations with plasmids containing any one of three of the ARSs (m24, m25, or m26) often contained extrachromosomal DNAs.


Ten-year outcomes of early generation sirolimus- versus paclitaxel-eluting stents in patients with left main coronary artery disease.
To compare 10-year outcomes after implantation of sirolimus-eluting stents (SES) versus paclitaxel-eluting stents (PES) for left main coronary artery (LMCA) stenosis. Very long-term outcome data of patients with LMCA disease treated with drug-eluting stents (DES) have not been well described. In 10-year extended follow-up of the MAINCOMPARE registry, we evaluated 778 patients with unprotected LMCA stenosis who were treated with SES (n = 607) or PES (n = 171) between January 2000 and June 2006. The primary composite outcome (a composite of death, myocardial infarction [MI] or target-vessel revascularization [TVR]) was compared with an inverse-probability-of-treatment-weighting (IPTW) adjustment. Clinical events have linearly accumulated over 10 years. At 10 years, there were no significant differences between SES and PES in the observed rates of the primary composite outcome (42.0% vs. 47.4%; hazard ratio [HR] 0.85; 95% confidence interval [CI] 0.66-1.10), and definite stent thrombosis (ST) (1.9% vs. 1.8%; HR 1.02, 95% CI 0.28-3.64). In the IPTW-adjusted analyses, there were no significant differences between SES and PES in the risks for the primary composite outcome (HR 0.89, 95% CI 0.65-1.14) or definite ST (adjusted HR 1.05, 95% CI 0.29-3.90). In patients who underwent DES implantation, high overall adverse clinical event rates (with a linearly increasing event rate over time) were observed during extended follow-up. At 10 years, there were no measurable differences in outcomes between patients treated with SES vs. PES for LMCA disease. The incidence of stent thrombosis was quite low and comparable between the groups.


Isoflavone Malonyltransferases GmIMaT1 and GmIMaT3 Differently Modify Isoflavone Glucosides in Soybean (Glycine max) under Various Stresses.
Malonylated isoflavones are the major forms of isoflavonoids in soybean plants, the genes responsible for their biosyntheses are not well understood, nor their physiological functions. Here we report a new benzylalcohol O-acetyltransferase, anthocyanin O-hydroxycinnamoyltransferase, anthranilate N-hydroxycinnamoyl/benzoyltransferase, deacetylvindoline 4-O-acetyltransferase (BAHD) family isoflavone glucoside malonyltransferase GmIMaT1, and GmIMaT3, which is allelic to the previously characterized GmMT7 and GmIF7MaT. Biochemical studies showed that recombinant GmIMaT1 and GmIMaT3 enzymes used malonyl-CoA and several isoflavone 7-O-glucosides as substrates. The Km values of GmIMaT1 for glycitin, genistin, and daidzin were 13.11, 23.04, and 36.28 μM, respectively, while these of GmIMaT3 were 12.94, 26.67, and 30.12 μM, respectively. Transgenic hairy roots overexpressing both GmIMaTs had increased levels of malonyldaidzin and malonylgenistin, and contents of daidzin and glycitin increased only in GmIMaT1-overexpression lines. The increased daidzein and genistein contents were detected only in GmIMaT3-overexpression lines. Knockdown of GmIMaT1 and GmIMaT3 reduced malonyldaidzin and malonylgenistin contents, and affected other isoflavonoids differently. GmIMaT1 is primarily localized to the endoplasmic reticulum while GmIMaT3 is primarily in the cytosol. By examining their transcript changes corresponding to the altered isoflavone metabolic profiles under various environmental and hormonal stresses, we probed the possible functions of GmIMaTs. Two GmIMaTs displayed distinct tissue expression patterns and respond differently to various factors in modifying isoflavone 7-O-glucosides under various stresses.


A comprehensive overview of the neuropsychiatry of Parkinson's disease: A review.
Parkinson's disease is a widespread neurological illness. However, its psychiatric links have also been discussed lately by many authors, which has brought more depth to the specialized field of neuropsychiatry. Neuropsychiatric complications are commonly seen in Parkinson's patients, including major depression, anxiety, psychosis and hallucination, and cognitive abnormality. Almost all of these complications have a distinct pathophysiology and treatment. In this article we review the most recent studies about the association of these symptoms with Parkinson's disease and highlight the epidemiology, diagnosis, pathophysiology, and treatment of the neuropsychiatric complications, with more emphasis on the pathophysiology of these complications.


Dental caries and erosion status of 12-year-old Hong Kong children.
This study aimed to assess the dental caries and erosion status of 12-year-old Hong Kong children and study the determinants of dental caries and dental erosion of these children. The survey was performed from 2011 to 2012 with ethics approval. Stratified random sampling was adopted to select 12-year-old children in 7 primary schools in Hong Kong. The participating parents were asked to complete a self-administered questionnaire concerning their children's diet and oral health habits. The children were examined for caries status with WHO criteria by 3 calibrated examiners. Detection of dental erosion followed Basic Erosive Wear Examination (BEWE) criteria. A total of 704 children were recruited and 600 (316 boys, 53%) participated in the survey. There were 124 children (21%) with caries experience (DMFT > 0) and their DMFT was 0.34 ± 0.76. About half of their decay was unfilled (DT = 0.16 ± 0.52) The DMFT of girls and boys were 0.45 ± 0.89 and 0.23 ± 0.61, respectively (p = 0.001). Girls also had a higher DT (0.21 ± 0.62 compared with 0.11 ± 0.41, p = 0.013) and FT than boys (0.23 ± 0.63 compared with 0.12 ± 0.44, p = 0.016). Most children (75%) had at least some sign of erosion (BEWE > 0), but no severe erosion (BEWE = 3). Logistic regression showed girls who consumed soft drinks and took vitamin C supplements had higher caries risk. Dental erosion was more severe among the children who had caries experience and consumed fruit juice. The 12-year-old Hong Kong children had low caries experience, and almost half of the decay was left untreated. Although severe erosion was not found, many children had early signs of erosion.


Vitamin D-binding protein deficiency in mice decreases systemic and select tissue levels of inflammatory cytokines in a murine model of acute muscle injury.
Severe acute muscle injury results in massive cell damage, causing the release of actin into extracellular fluids where it complexes with the vitamin D-binding protein (DBP). We hypothesized that a systemic DBP deficiency would result in a less proinflammatory phenotype. C57BL/6 wild-type (WT) and DBP-deficient (DBP-/-) mice received intramuscular injections of either 50% glycerol or phosphate-buffered saline into thigh muscles. Muscle injury was assessed by histology. Cytokine levels were measured in plasma, muscle, kidney, and lung. All animals survived the procedure, but glycerol injection in both strains of mice showed lysis of skeletal myocytes and inflammatory cell infiltrate. The muscle inflammatory cell infiltrate in DBP-deficient mice had remarkably few neutrophils as compared with WT mice. The neutrophil chemoattractant CXCL1 was significantly reduced in muscle tissue from DBP-/- mice. However, there were no other significant differences in muscle cytokine levels. In contrast, plasma obtained 48 hours after glycerol injection revealed that DBP-deficient mice had significantly lower levels of systemic cytokines interleukin 6, CCL2, CXCL1, and granulocyte colony-stimulating factor. Lung tissue from DBP-/- mice showed significantly decreased amounts of CCL2 and CXCL1 as compared with glycerol-treated WT mice. Several chemokines in kidney homogenates following glycerol-induced injury were significantly reduced in DBP-/- mice: CCL2, CCL5, CXCL1, and CXCL2. Acute muscle injury triggered a systemic proinflammatory response as noted by elevated plasma cytokine levels. However, mice with a systemic DBP deficiency demonstrated a change in their cytokine profile 48 hours after muscle injury to a less proinflammatory phenotype.


Cardiac performance in the conscious rabbit with acute hypertension following brainstem lesions coinciding with the A1 group of catecholamine neurons.
Electrolytic lesions of the ventrolateral medulla, coinciding with the A1 catecholamine cells of the conscious rabbit (A1 lesions) cause acute hypertension and bradycardia and in some animals, pulmonary oedema. We have assessed the change in cardiac performance after an A1 lesion, the role of cardiac autonomic effectors in this change; and the mechanism of the pulmonary oedema. Following A1 lesions there was a profound (over 100%) rise in total peripheral resistance and a fall in cardiac output which was mainly due to a fall in stroke volume since it occurred even in animals in which the heart rate was held constant by atrial pacing. This reduced stroke volume occurred despite a 40% increase in myocardial contractility (peak LV dP/dt) and elevation of left ventricular end diastolic pressure. beta-Adrenoceptor blockade with propranolol abolished the rise in peak LV dP/dt, while vagal blockade with methylscopolamine abolished the bradycardia and combined blockade with propranolol and methylscopolamine abolished the rise in peak LV dP/dt and reduced the bradycardia. In rabbits which developed pulmonary oedema, left ventricular end diastolic pressure rose to 35 +/- 3.5 compared to 16 +/- 2.7 mmHg in those which did not, suggesting that the pulmonary oedema was due to raised left ventricular filling pressure.


The complete sequence of mitochondrial genome of Wuzhishan pig (Sus Scrofa).
In the present study, we sequenced the complete mitochondrial genome of Wuzhishan pig, which was 16,741 bp in size and had a nucleotide composition in A and T (60.46%). The genome consisted of a major non-coding control region (D-loop region) and 37 genes, including 2 ribosomal RNA (rRNA) genes, 13 protein-coding genes (PCGs), and 22 transfer RNA (tRNA) genes. The genes in the mitochondrial genomes of Wuzhishan pig used three kinds of initiation codons (ATA, ATG, and GTG) and four kinds of termination codons (TAA, AGA, TAG, and an incomplete termination codons T-). The complete mitochondrial genome sequence of Wuzhishan pig provides an important data set for further study on genetic mechanism.


Homology and evolution of the antenna in podocopid ostracods from the perspective of aesthetascs.
Antennal podomere homology has not been well documented in podocopid ostracods. Difficulties associated with describing this homology are compounded by the occurrence of specialised podomeres in both cytheroids and bairdioids. Our research establishes the existence of two kinds of aesthetascs shared among multiple higher taxa. Overgrowth "t-setae" are present in males in Cytheroidea, Cypridocopina and Darwinuloidea, and "aesthetasc yc" is found in both sexes in Cytheroidea and Bairdioidea. Homology of the antennal podomeres among all podocopid superfamilies was determined by using the chaetotaxy of these aesthetascs, leading to a description of evolutionary modifications of the podocopid antenna, which suggests that changes in function of the articulation were prompted by the temporal demands of copulatory behavior in each lineage.


The genetics of axonal transport and axonal transport disorders.
Neurons are specialized cells with a complex architecture that includes elaborate dendritic branches and a long, narrow axon that extends from the cell body to the synaptic terminal. The organized transport of essential biological materials throughout the neuron is required to support its growth, function, and viability. In this review, we focus on insights that have emerged from the genetic analysis of long-distance axonal transport between the cell body and the synaptic terminal. We also discuss recent genetic evidence that supports the hypothesis that disruptions in axonal transport may cause or dramatically contribute to neurodegenerative diseases.


SEXUAL SELECTION, VIABILITY SELECTION, AND DEVELOPMENTAL STABILITY IN THE DOMESTIC FLY MUSCA DOMESTICA.
Associations between developmental stability, sexual selection, and viability selection were studied in the domestic fly Musca domestica (Diptera, Muscidae). Developmental stability of the wings and tibia of flies of both sexes, measured in terms of their level of fluctuating asymmetry, was positively associated with mating success in free ranging populations and in sexual selection experiments. Mated individuals may have obtained indirect fitness benefits from sexual selection of two different kinds. First, the entomopathogenic fungus Enthomophthora muscae (Zygomycetes, Entomophthorales) infects and kills adult domestic flies, and flies dead from fungus infections had more asymmetric wings than flies dead for other reasons. Experimental deposition of fungus spores on uninfected flies demonstrated that flies with asymmetric wings were more susceptible to fungus infections than flies with symmetric wings. Second, domestic flies were frequently eaten by insectivorous barn swallows Hirundo rustica, and flies depredated by birds had more asymmetric wings and tibia than surviving flies.


Ionization of aromatic sulfides in nonpolar media: free vs reaction-controlled electron transfer.
The primary products of the bimolecular free electron transfer (FET) from aromatic sulfides (PhSCH2Ph, PhSCHPh2, PhSCPh3) to n-butyl chloride radical cations are two radical cation conformers: a dissociative and a metastable one. In analogy with formerly studied donor systems, this result seems to reflect femtosecond oscillations in the ground state of the sulfides such as torsion motions around the Ar-S bond. This motion is accompanied by a marked electron fluctuation within the HOMO (or the n) orbitals. The FET products observed in the nanosecond time scale such as the metastable sulfide radical cations (Ar-S-CR3*+), the dissociation products R3C+; and R3C*, and their (experimentally) nondetectable counterparts Ar-S* as well as Ar-S+ can be understood with the simplified assumption of two extreme conformations, namely a planar and a twisted donor molecule. Using mediator radical cations (benzene, butylbenzene, biphenyl), the stepwise reduction of the free energy of the electron transfer from -DeltaH = 2.5 to <or=0.5 eV changes the dissociation pattern of the sulfide radical cations toward a uniform product such as the metastable sulfide radical cation. From that, we tentatively interpret the mechanism of the studied electron transfer as diffusion-controlled (collision-determined FET) at higher -DeltaH values and as reaction-controlled at -DeltaH below 0.5 eV.


Dendrimeric organochalcogen catalysts for the activation of hydrogen peroxide: origins of the "dendrimer effect" with catalysts terminating in phenylseleno groups.
Several scenarios were evaluated to explain the large "dendrimer effect" observed in the bromination of cyclohexene with H(2)O(2) and NaBr catalyzed by the addition of Frechét-type dendrimers terminating in -O(CH(2))(3)SePh groups. Although phenylseleninic acid was an efficient catalyst for the oxidation of NaBr with H(2)O(2), first-order rate constants for the selenoxide elimination were too small to produce PhSeO(2)H at a rate sufficient to explain the rates of catalysis and no dendrimer effect was observed in the rates of selenoxide elimination. An induction period was observed using 1-SePh as a catalyst for the oxidation of Br(-) with H(2)O(2). The addition of preformed selenoxide 1-Se(=O)Ph gave immediate catalysis with no induction period. However, rates of oxidation of the selenides with H(2)O(2) under homogeneous or biphasic conditions or with t-BuOOH under homogeneous conditions were too slow to account for the rates of catalysis, and no dendrimer effect was observed in the rates of oxidation. The primary oxidant for converting selenides to selenoxides was "Br(+)" produced initially by the uncatalyzed background reaction of H(2)O(2) with NaBr and then produced catalytically following formation of selenoxide groups. Autocatalysis is observed, and the rate of oxidation increases with the number of SePh groups. Autocatalysis is the source of the large dendrimer effect observed with the SePh series of catalysts.


Atypical Presentation of Gouty Tophus as Posterior Cruciate Ligament Cyst: A Case Report.
Gouty tophi generally develop around 10 years after the first attack of gout in untreated patients and are commonly found around feet, hands, and elbows. However, tophi can also occur as first sign of disorder. Tophaceous gout presenting in young at the posterior cruciate ligament (PCL) is extremely rare and difficult to diagnose because of its atypical presentation and no hallmark features in magnetic resonance imaging (MRI). Here, we report a 25-year-old man manual worker with no prior history of gout has presented with left knee pain and locking episodes for 3 weeks, X-ray shows no abnormality, on advanced imaging with MRI, a well-defined cyst noted adjacent to PCL toward lateral aspect. During arthroscopy, a cyst was seen between anterior cruciate ligament and PCL with the extrusion of chalky paste-like material on puncturing the cyst. The tophus was biopsied and excised arthroscopically with excellent outcome. This case report demonstrates that gout does not only always cause severe joint pain from inflammatory arthritis, but can also cause mechanical pain and locking of joint atypically presenting as intra-articular tophi. Hence, gout should also be considered in differential diagnosis of intra-articular cyst. Arthroscopic removal and continuous urate-lowering therapy provide excellent outcomes for such atypical presentations.


Models of growth hormone and IGF-1 deficiency: applications to studies of aging processes and life-span determination.
The remarkable progress in understanding the genetic basis of life-span determination in invertebrates indicates that impairments in the insulin-insulin-like growth factor 1 (IGF-1) signaling cascade increase longevity. Similarities among insulin and IGF-1-like signaling pathways in invertebrates and mammals raise the possibility that modifications of these pathways may extend life span in mammals. Investigators using Ames, Snell, and growth hormone receptor knockout models have concluded that decreased growth hormone and IGF-1 are responsible for increased life span. In this review, we critique the dwarf models and, based on multiple endocrine deficiencies and developmental anomalies, conclude that these models may not be sufficient to assess the consequences of growth hormone or IGF-1 deficiency on either biological aging or life span. We attempt to resolve some of these issues by presenting an alternative animal model of growth hormone-IGF-1 deficiency. Finally, we propose an integrated explanation of growth hormone and IGF-1's contribution to the aging phenotype and life-span determination.


Automatic Detection of Mitosis and Nuclei From Cytogenetic Images by CellProfiler Software for Mitotic Index Estimation.
Mitotic Index (MI) estimation expressed as percentage of mitosis plays an important role as quality control endpoint. To this end, MI is applied to check the lot of media and reagents to be used throughout the assay and also to check cellular viability after blood sample shipping, indicating satisfactory/unsatisfactory conditions for the progression of cell culture. The objective of this paper was to apply the CellProfiler open-source software for automatic detection of mitotic and nuclei figures from digitized images of cultured human lymphocytes for MI assessment, and to compare its performance to that performed through semi-automatic and visual detection. Lymphocytes were irradiated and cultured for mitosis detection. Sets of images from cultures were analyzed visually and findings were compared with those using CellProfiler software. The CellProfiler pipeline includes the detection of nuclei and mitosis with 80% sensitivity and more than 99% specificity. We conclude that CellProfiler is a reliable tool for counting mitosis and nuclei from cytogenetic images, saves considerable time compared to manual operation and reduces the variability derived from the scoring criteria of different scorers. The CellProfiler automated pipeline achieves good agreement with visual counting workflow, i.e. it allows fully automated mitotic and nuclei scoring in cytogenetic images yielding reliable information with minimal user intervention.


Endopolyploidy is a common response to UV-B stress in natural plant populations, but its magnitude may be affected by chromosome type.
Ultraviolet-B radiation (UV-B) radiation damages the DNA, cells and photosynthetic apparatus of plants. Plants commonly prevent this damage by synthetizing UV-B-protective compounds. Recent laboratory experiments in Arabidopsis and cucumber have indicated that plants can also respond to UV-B stress with endopolyploidy. Here we test the generality of this response in natural plant populations, considering their monocentric or holocentric chromosomal structure. We measured the endopolyploidy index (flow cytometry) and the concentration of UV-B-protective compounds in leaves of 12 herbaceous species (1007 individuals) from forest interiors and neighbouring clearings where they were exposed to increased UV-B radiation (103 forest + clearing populations). We then analysed the data using phylogenetic mixed models. The concentration of UV-B protectives increased with UV-B doses estimated from hemispheric photographs of the sky above sample collection sites, but the increase was more rapid in species with monocentric chromosomes. Endopolyploidy index increased with UV-B doses and with concentrations of UV-B-absorbing compounds only in species with monocentric chromosomes, while holocentric species responded negligibly. Endopolyploidy seems to be a common response to increased UV-B in monocentric plants. Low sensitivity to UV-B in holocentric species might relate to their success in high-UV-stressed habitats and corroborates the hypothesized role of holocentric chromosomes in plant terrestrialization.


Radiation dose to premature infants in neonatal intensive care units in Kuwait.
Entrance surface dose (ESD) and effective dose (E) to premature infants were estimated at three neonatal intensive care units in Kuwait for three standard X-ray examinations--abdominal, chest and skull X rays using a simple water phantom. The ESD was found to vary between 58 and 102 microGy for abdominal X rays, between 51 and 102 microGy for chest X rays and between 58 and 145 microGy for skull examinations. These doses are comparable to the entrance skin doses published elsewhere. The E-values were estimated using normalised organ dose dataset from the National Radiological Protection Board. The E-values for abdominal, chest and skull examinations were in the ranges of 30-46, 20-36 and 8-18 microSv per examination, respectively. The risk of developing childhood cancers from each of the three examinations was estimated to be in the range (9-117) x 10(-6) for infants undergoing 25 of these X-ray examinations during their stay in the NIC unit.


A Rare Presentation of Lisegang Rings in Adrenal Cavernous Hemangioma : Case Report and Literature Review.
Adrenal cavernous hemangiomas (AH) are benign nonfunctional vascular tumors rarely discovered as incidental findings on imaging studies or autopsies. This study presents a single case report of AH with another rare finding of the Liesegang ring. Also, we reviewed 73 case reports of cavernous adrenal hemangioma to provide an overview of AH's clinical characteristics. Case Report. A nonfunctional AH was incidentally discovered in a 59-year-old morbidly obese female patient with a 10-year history of hypertension and thyroidectomy. An abdominal computed tomography (CT) scan showed a left suprarenal mass of ∼16 cm in diameter. While the patient had no clinical manifestations from the hemangioma, all laboratory tests were within the normal values with no indication of a functional adrenal tumor. The mass was removed by open left adrenalectomy. The microscopic histological examination revealed a laminated structure with wide blood-filled spaces with a central core of necrotic and hemorrhagic changes, characteristic of a cavernous AH with the presence of a rare Liesegang ring. Although rare, AH should be considered as a differential diagnosis for adrenal masses. This is the first reported case of a cavernous AH with rare microscopic findings of the Liesegang ring.